Vanilloid receptor ligands and their use in treatments

ABSTRACT

Compounds having the general structure  
                 
and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

This application claims the benefit of U.S. Provisional Application No.60/507,863, filed Sep. 30, 2003, which is hereby incorporated byreference.

BACKGROUND

The vanilloid receptor 1 (VR1) is the molecular target of capsaicin, theactive ingredient in hot peppers. Julius et al. reported the molecularcloning of VR1 (Caterina et al., 1997). VR1 is a non-selective cationchannel which is activated or sensitized by a series of differentstimuli including capsaicin and resiniferatoxin (exogenous activators),heat & acid stimulation and products of lipid bilayer metabolism,anandamide (Premkumar et al., 2000, —Szabo et al., 2000, Gauldie et al.,2001, —Olah et al., 2001) and lipoxygenase metabolites (Hwang et al.,2000). VR1 is highly expressed in primary sensory neurons (Caterina etal., 1997) in rats, mice and humans (Onozawa et al., 2000, Mezey et al.,2000, Helliwell et al., 1998, —Cortright et al., 2001). These sensoryneurons innervate many visceral organs including the dermis, bones,bladder, gastrointestinal tract and lungs; VR1 is also expressed inother neuronal and non-neuronal tissues including but not limited to,CNS nuclei, kidney, stomach and T-cells (Nozawa et al., 2001, —Yiangouet al., 2001, —Birder et al., 2001). Presumably expression in thesevarious cells and organs may contribute to their basic properties suchas cellular signaling and cell division.

Prior to the molecular cloning of VR1, experimentation with capsaicinindicated the presence of a capsaicin sensitive receptor, which couldincrease the activity of sensory neurons in humans, rats and mice(Holzer, 1991; Dray, 1992, Szallasi and Blumberg 1996, 1999). The resultof acute activation by capsaicin in humans was pain at injection siteand in other species increased behavioral sensitivity to sensory stimuli(Szallasi and Blumberg, 1999). Capsaicin application to the skin inhumans causes a painful reaction characterized not only by theperception of heat and pain at the site of administration but also by awider area of hyperalgesia and allodynia, two characteristic symptoms ofthe human condition of neuropathic pain (Holzer, 1991). Taken together,it seems likely that increased activity of VR1 plays a significant rolein the establishment and maintenance of pain conditions. Topical orintradermal injection of capsaicin has also been shown to producelocalized vasodilation and edema production (Szallasi and Blumberg 1999,—Singh et al., 2001). This evidence indicates that capsaicin throughit's activation of VR1 can regulate afferent and efferent function ofsensory nerves. Sensory nerve involvement in diseases could therefore bemodified by molecules, which affect the function of the vanilloidreceptor to increase or decrease the activity of sensory nerves.

VR1 gene knockout mice have been shown to reduce sensory sensitivity tothermal and acid stimuli (Caterina et al., 2000)). This supports theconcept that VR1 contributes not only to generation of pain responses(i.e. via thermal, acid or capsaicin stimuli) but also to themaintenance of basal activity of sensory nerves. This evidence agreeswith studies demonstrating capsaicin sensitive nerve involvement indisease. Primary sensory nerves in humans and other species can be madeinactive by continued capsaicin stimulation. This paradigm causesreceptor activation induced desensitization of the primary sensorynerve - such reduction in sensory nerve activity in vivo makes subjectsless sensitive to subsequent painful stimuli. In this regard bothcapsaicin and resinferatoxin (exogenous activators of VR1), producedesensitization and they have been used for many proof of conceptstudies in in vivo models of disease (Holzer, 1991, Dray 1992, —Szallasiand Blumberg 1999).

BIBLIOGRAPHY

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SUMMARY

The present invention comprises a new class of compounds useful in thetreatment of diseases, such as vanilloid-receptor-mediated diseases andother maladies, such as inflammatory or neuropathic pain and diseasesinvolving sensory nerve function such as asthma, rheumatoid arthritis,osteoarthritis, inflammatory bowel disorders, urinary incontinence,migraine and psoriasis. In particular, the compounds of the inventionare useful for the treatment of acute, inflammatory and neuropathicpain, dental pain, general headache, migraine, cluster headache,mixed-vascular and non-vascular syndromes, tension headache, generalinflammation, arthritis, rheumatic diseases, osteoarthritis,inflammatory bowel disorders, inflammatory eye disorders, inflammatoryor unstable bladder disorders, psoriasis, skin complaints withinflammatory components, chronic inflammatory conditions, inflammatorypain and associated hyperalgesia and allodynia, neuropathic pain andassociated hyperalgesia and allodynia, diabetic neuropathy pain,causalgia, sympathetically maintained pain, deafferentation syndromes,asthma, epithelial tissue damage or dysfunction, herpes simplex,disturbances of visceral motility at respiratory, genitourinary,gastrointestinal or vascular regions, wounds, burns, allergic skinreactions, pruritus, vitiligo, general gastrointestinal disorders,gastric ulceration, duodenal ulcers, diarrhea, gastric lesions inducedby necrotising agents, hair growth, vasomotor or allergic rhinitis,bronchial disorders or bladder disorders. Accordingly, the inventionalso comprises pharmaceutical compositions comprising the compounds,methods for the treatment of vanilloid-receptor-mediated diseases, suchas inflammatory or neuropathic pain, asthma, rheumatoid arthritis,osteoarthritis, inflammatory bowel disorders, urinary incontinence,migraine and psoriasis diseases, using the compounds and compositions ofthe invention, and intermediates and processes useful for thepreparation of the compounds of the invention.

The compounds of the invention are represented by the following generalstructure:

or a pharmaceutically acceptable salt thereof, wherein J, R¹, R², R⁴,R^(d), X, Y and Z are defined below.

The foregoing merely summarizes certain aspects of the invention and isnot intended, nor should it be construed, as limiting the invention inany way. All patents, patent applications and other publications recitedherein are hereby incorporated by reference in their entirety.

DETAILED DESCRIPTION

One aspect of the current invention relates to compounds having thegeneral structure:

or any pharmaceutically-acceptable salt thereof, wherein:

-   -   J is NH, O or S;    -   X is N or C(R²);    -   Y is N or C(R³), wherein at least one of X and Y is N;    -   Z is C(R^(d)), or if X is C(R²), then Z is N or C(R^(d));    -   n is independently, at each instance, 0, 1 or 2.    -   R¹ is a saturated, partially-saturated or unsaturated 5-, 6- or        7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered        vicinally-fused bicyclic ring containing 0, 1, 2, 3 or 4 atoms        selected from N, O and S, so long as the combination of O and S        atoms is not greater than 2, wherein the carbon atoms of the        ring are substituted by 0, 1 or 2 oxo or thioxo groups, wherein        the ring is substituted by 0, 1, 2, 3 or 4 substituents selected        from C₁₋₈alkyl, halo, C₁₋₄haloalkyl, cyano, nitro, —C(═O)R^(e),        —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),        —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),        —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),        —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),        —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),        —NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),        —N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)NR^(f), —NR^(a)C₂₋₆alkylOR^(f),        —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),        —C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h),        —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),        —OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h),        —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h), —S(═O)₂R^(h),        —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),        —S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),        —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h),        —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f),        —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),        —N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),        —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(h),        —N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and        —NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted        by 0 or 1 saturated, partially-saturated or unsaturated 5-, 6-        or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered        vicinally-fused bicyclic ring containing 0, 1, 2, 3 or 4 atoms        selected from N, O and S, so long as the combination of O and S        atoms is not greater than 2, wherein the carbon atoms of the        ring are substituted by 0, 1 or 2 oxo or thioxo groups, wherein        the ring is substituted by 0, 1, 2 or 3 groups selected from        R^(e), halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),        —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),        —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),        —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),        —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),        —NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),        —N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f),        —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),        —C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h),        —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),        —OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h),        —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h), —S(═O)₂R^(h),        —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),        —S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),        —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h),        —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f),        —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),        —N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),        —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),        —N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and        —NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted        by 0 or 1 C₁₋₄alkyl groups substituted by 1, 2 or 3 groups        selected from C₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e),        —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),        —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),        —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),        —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),        —NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),        —N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂ NR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f),        —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(f),        —C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h),        —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),        —OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h),        —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h), —S(═O)₂R^(h),        —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),        —S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),        —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h),        —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f),        —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),        —N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),        —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),        —N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and        —NR^(a)C₂₋₆alkylOR^(h); wherein R¹ is not tetrazole;    -   R² is, independently, in each instance, selected from H,        C₁₋₈alkyl, halo, C₁₋₄haloalkyl, cyano, nitro, —C(═O)R^(e),        —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),        —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),        —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),        —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),        —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),        —NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),        —N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂ NR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f),        —C(═O)R^(f), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),        —C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h),        —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),        —OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h),        —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h), —S(═O)₂R^(h),        —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),        —S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),        —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h),        —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f),        —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),        —N(R^(h))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),        —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),        —N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and        —NR^(a)C₂₋₆alkylOR^(h) or R² is a saturated, partially-saturated        or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-,        9-, 10- or 11-membered vicinally-fused bicyclic ring containing        0, 1, 2, 3 or 4 atoms selected from N, O and S, so long as the        combination of O and S atoms is not greater than 2, wherein the        carbon atoms of the ring are substituted by 0, 1 or 2 oxo or        thioxo groups, wherein the ring is substituted by 0, 1, 2 or 3        groups selected from R^(e), halo, cyano, nitro, —C(═O)R^(e),        —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),        —OR^(e), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),        —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),        —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),        —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),        —NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),        —N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f),        —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(f),        —C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h),        —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),        —OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h),        —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h), —S(═O)₂R^(h) ,        —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),        —S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),        —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h),        —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h), —N(R^(a))C(═O)OR^(f),        —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),        —N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),        —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),        —N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and        —NR^(a)C₂₋₆alkylOR^(h)or R² is C₁₋₄alkyl substituted by 0, 1, 2        or 3 groups selected from C₁₋₄haloalkyl, halo, cyano, nitro,        —C(═O)R^(e), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),        —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),        —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),        —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),        —NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),        —N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f),        —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),        —C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h),        —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),        —OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h),        —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h), —S(═O)₂R^(h),        —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),        —S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),        —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h),        —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f),        —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),        —N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),        —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),        —N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and        —NR^(a)C₂₋₆alkylOR^(h);    -   R³ is, independently, in each instance, H, halo, —NH₂,        —NHC₁₋₃alkyl, —N(C₁₋₃alkyl)C₁₋₃alkyl, or C₁₋₃alkyl;    -   R⁴ is a saturated, partially-saturated or unsaturated 5-, 6- or        7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered        vicinally-fused bicyclic ring containing 0, 1, 2, 3 or 4 atoms        selected from N, O and S, so long as the combination of O and S        atoms is not greater than 2, wherein the carbon atoms of the        ring are substituted by 0, 1 or 2 oxo or thioxo groups, wherein        the ring is substituted by 0, 1, 2, 3 or 4 substituents selected        from C₁₋₈alkyl, C₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e),        —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),        —OR^(f), —OC(═O)R^(e), —C(═O)NR^(a)R^(f),        —OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),        —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),        —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),        —S(═O)₂N(R^(f))C(═O)OR^(f).—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),        —NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),        —N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),        —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),        —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),        —C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h),        —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),        —OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h),        —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h), —S(═O)₂R^(h),        —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),        —S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),        —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h),        —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f),        —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),        —N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),        —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),        —N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and        —NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally        substuted by C₁₋₄alkyl substituted by 1, 2 or 3 substituents        selected from halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),        —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),        —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e),        —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),        —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),        —S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),        —NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),        —N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),        —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f).—C(═O)R^(h),        —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),        —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),        —OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),        —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),        —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),        —S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),        —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h),        —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f),        —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),        —N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),        —N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),        —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),        —N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆akylNR^(a)R^(f),        —NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and        —NR^(a)C₂₋₆alkylOR^(h); wherein R⁴ is not pyrrolidine or        pyrazole;    -   R^(a) is independently, at each instance, H, phenyl, benzyl or        C₁₋₆alkyl, the phenyl, benzyl and C₁₋₆alkyl being substituted by        0, 1, 2 or 3 substituents selected from halo, C₁₋₄alkyl,        C₁₋₃haloalkyl, —OC₁₋₄alkyl, —NH₂, —NHC₁₋₄alkyl,        —N(C₁₋₄alkyl)C₁₋₄alkyl;    -   R^(d) is independently in each instance hydrogen or —CH₃;    -   R^(e) is, independently, in each instance, C₁₋₉alkyl or        C₁₋₄alkyl(phenyl) wherein either is substituted by 0, 1, 2, 3 or        4 substituents selected from halo, C₁₋₄haloalkyl, cyano, nitro,        —C(═O)R^(e), —C(═O)OR^(e), —C(═O)NR^(a)R^(a),        —C(═NR^(a))NR^(a)R^(a), —OR^(a), —OC(═O)R^(e),        —OC(═O)NR^(a)R^(a), —OC(═O)N(R^(a))S(═O)₂R^(e),        —OC₂₋₆alkylNR^(a)R^(a), —OC₂₋₆alkylOR^(a), —SR^(a), —S(═O)R^(e),        —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(a), —S(═O)₂N(R^(a))C(═O)R^(e),        —S(═O)₂N(R^(a))C(═O)OR^(e), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(a),        —NR^(a)R^(a), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(e),        —N(R^(a))C(═O)NR^(a)R^(a), —N(R^(a))C(═NR^(a))NR^(a)R^(a),        —N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(a),        —NR^(a)C₂₋₆alkylNR^(a)R^(a) and —NR^(a)C₂₋₆alkylOR^(a); and        wherein the C₁₋₉alkyl is additionally substituted by 0 or 1        groups independently selected from R^(h);    -   R^(f) is, independently, in each instance, R^(e) or H;    -   R^(g) is, independently, in each instance, a saturated or        unsaturated 5- or 6-membered monocyclic ring containing 1, 2 or        3 atoms selected from N, O and S, so long as the combination of        O and S atoms is not greater than 2, wherein the ring is        substituted by 0 or 1 oxo or thioxo groups; and

-   R^(h) is, independently, in each instance, phenyl or a saturated or    unsaturated 5- or 6-membered monocyclic ring containing 1, 2 or 3    atoms selected from N, O and S, so long as the combination of O and    S atoms is not greater than 2, wherein the ring is substituted by 0    or 1 oxo or thioxo groups, wherein the phenyl or monocycle are    substituted by 0, 1, 2 or 3 substituents selected from halo, cyano,    nitro, —C(═O)R^(e), —C(═O)OR^(e), —C(═O)NR^(a)R^(f),    —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),    —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),    —OC₂₋₆alkylOR^(f), —SR^(f), —S(═O)R^(e), —S(═O)₂R^(e),    —S(═O)₂NR^(a)R^(f).—S(═O)₂N(R^(a))C(═O)R^(e),    —S(═O)₂N(R^(a))C(═O)OR^(e), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),    —NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(e),    —N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),    —N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),    —NR^(a)C₂₋₆alkylNR^(a)R^(f) and —NR^(a)C₂₋₆alkylOR^(f).

In another embodiment, in conjunction with any one of the above andbelow embodiments, X is C(R²); Y is N; and Z is C(R^(d)).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R¹ is a ring selected from thiophene, pyrrole,1,3-oxazole, 1,3-thiazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole,1,2,3-oxadiazole, 1,2,3-thiadiazole, 1H-1,2,3-triazole, isothiazole,1,2,4-oxadiazole, 1,2,4-thiadiazole, 1,2,3,4-oxatriazole,1,2,3,4-thiatriazole, 1H-1,2,3,4-tetraazole, 1,2,3,5-oxatriazole,1,2,3,5-thiatriazole, furan, imidazol-1-yl, imidazol-4-yl,1,2,4-triazol-4-yl, 1,2,4-triazol-5-yl, isoxazol-3-yl, isoxazol-5-yl,pyrazol-3-yl, pyrazol-5-yl, thiolane, pyrrolidine, tetrahydrofuran,4,5-dihydrothiophene, 2-pyrroline, 4,5-dihydrofuran, pyridazine,pyrimidine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,2,4-triazine,1,3,5-triazine, pyridine, 2H-3,4,5,6-tetrahydropyran, thiane,1,2-diazaperhydroine, 1,3-diazaperhydroine, piperazine,1,3-oxazaperhydroine, morpholine, 1,3-thiazaperhydroine,1,4-thiazaperhydroine, piperidine, 2H-3,4-dihydropyran,2,3-dihydro-4H-thiin, 1,4,5,6-tetrahydropyridine, 2H-5,6-dihydropyran,2,3-dihydro-6H-thiin, 1,2,5,6-tetrahydropyridine,3,4,5,6-tetrahydropyridine, 4H-pyran, 4H-thiin, 1,4-dihydropyridine,1,4-dithiane, 1,4-dioxane, 1,4-oxathiane, 1,2-oxazolidine,1,2-thiazolidine, pyrazolidine, 1,3-oxazolidine, 1,3-thiazolidine,imidazolidine, 1,2,4-oxadiazolidine, 1,3,4-oxadiazolidine,1,2,4-thiadiazolidine, 1,3,4-thiadiazolidine, 1,2,4-triazolidine,2-imidazoline, 3-imidazoline, 2-pyrazoline, 4-imidazoline,2,3-dihydroisothiazole, 4,5-dihydroisoxazole, 4,5-dihydroisothiazole,2,5-dihydroisoxazole, 2,5-dihydroisothiazole, 2,3-dihydroisoxazole,4,5-dihydrooxazole, 2,3-dihydrooxazole, 2,5-dihydrooxazole,4,5-dihydrothiazole, 2,3-dihydrothiazole,, 2,5-dihydrothiazole,1,3,4-oxathiazolidine, 1,4,2-oxathiazolidine,2,3-dihydro-1H-[1,2,3]triazole, 2,5-dihydro-1H-[1,2,3]triazole,4,5-dihydro-1H-[1,2,3]triazole, 2,3-dihydro-1H-[1 ,2,4]triazole,4,5-dihydro-1H-[1,2,4]triazole, 2,3-dihydro-[1,2,4]oxadiazole,2,5-dihydro-[1,2,4]oxadiazole, 4,5-dihydro-[1,2,4]thiadiazole,2,3-dihydro-[1,2,4] thidiazole, 2,5-dihydro-[1,2,4] thiadiazole,4,5-dihydro-[1,2,4] thiadiazole, 2,5-dihydro-[1,2,4]oxadiazole,2,3-dihydro-[1,2,4]oxadiazole, 4,5-dihydro-[1,2,4]oxadiazole,2,5-dihydro-[1,2,4]thiadiazole, 2,3-dihydro-[1,2,4] thiadiazole,4,5-dihydro-[1,2,4] thiadiazole, 2,3-dihydro-[1,3,4]oxadiazole,2,3-dihydro-[1,3,4]thiadiazole, [1,4,2]oxathiazole, [1,3,4]oxathiazole,1,3,5-triazaperhydroine, 1,2,4-triazaperhydroine,1,4,2-dithiazaperhydroine, 1,4,2-dioxazaperhydroine,1,3,5-oxadiazaperhydroine, 1,2,5-oxadiazaperhydroine,1,3,4-thiadiazaperhydroine, 1,3,5-thiadiazaperhydroine,1,2,5-thiadiazaperhydroine, 1,3,4-oxadiazaperhydroine,1,4,3-oxathiazaperhydroine, 1,4,2-oxathiazaperhydroine,1,4,5,6-tetrahydropyridazine, 1,2,3,4-tetrahydropyridazine,1,2,3,6-tetrahydropyridazine, 1,2,5,6-tetrahydropyrimidine,1,2,3,4-tetrahydropyrimidine, 1,4,5,6-tetrahydropyrimidine,1,2,3,6-tetrahydropyrazine, 1,2,3,4-tetrahydropyrazine,5,6-dihydro-4H-[1,2]oxazine, 5,6-dihydro-2H-[1,2]oxazine,3,6-dihydro-2H-[1,2]oxazine, 3,4-dihydro-2H-[1,2]oxazine,5,6-dihydro-4H-[1,2]thiazine, 5,6-dihydro-2H-[1,2] thiazine,3,6-dihydro-2H-[1,2] thiazine, 3,4-dihydro-2H-[1,2] thiazine,5,6-dihydro-2H-[1,3]oxazine, 5,6-dihydro-4H-[1,3]oxazine,3,6-dihydro-2H-[1,3]oxazine, 3,4-dihydro-2H-[1 ,3]oxazine,3,6-dihydro-2H-[1,4]oxazine, 3,4-dihydro-2H-[1,4]oxazine,5,6-dihydro-2H-[1,3]thiazine, 5,6-dihydro-4H-[1,3]thiazine,3,6-dihydro-2H-[1 ,3]thiazine, 3,4-dihydro-2H-[1,3]thiazine,3,6-dihydro-2H-[1,4]thiazine, 3,4-dihydro-2H-[1,4]thiazine,1,2,3,6-tetrahydro-[1,2,4]triazine, 1,2,3,4-tetrahydro-[1,2,4]triazine,1,2,3,4-tetrahydro-[1,3,5]triazine, 2,3,4,5-tetrahydro-[1,2,4]triazine,1,4,5,6-tetrahydro-[1,2,4]triazine, 5,6-dihydro-[1,4,2]dioxazine,5,6-dihydro-[1,4,2]dioxazine, 5,6-dihydro-[1,4,2]dithiazine,2,3-dihydro-[1,4,2]dioxazine, 3,4-dihydro-2H-[1,3,4]oxadiazine,3,6-dihydro-2H-[1,3,4]oxadiazine, 3,4-dihydro-2H-[1,3,5]oxadiazine,3,6-dihydro-2H-[1,3,5]oxadiazine, 5,6-dihydro-2H-[1,2,5]oxadiazine,5,6-dihydro-4H-[1,2,5]oxadiazine, 3,4-dihydro-2H-[1,3,4]thiadiazine,3,6-dihydro-2H-[1,3,4]thiadiazine, 3,4-dihydro-2H-[1,3,5]thiadiazine,3,6-dihydro-2H-[1,3,5]thiadiazine, 5,6-dihydro-2H-[1,2,5]thiadiazine,5,6-dihydro-4H-[1,2,5]thiadiazine, 5,6-dihydro-2H-[1,2,3]oxadiazine,3,6-dihydro-2H-[1,2,5]oxadiazine, 5,6-dihydro-4H-[1,3,4]oxadiazine,3,4-dihydro-2H-[1,2,5]oxadiazine, 5,6-dihydro-2H-[1,2,3]thiadiazine,3,6-dihydro-2H-[1,2,5]thiadiazine, 5,6-dihydro-4H-[1,3,4]thiadiazine,3,4-dihydro-2H-[1,2,5]thiadiazine, 5,6-dihydro-[1,4,3]oxathiazine,5,6-dihydro-[1,4,2]oxathiazine, 2,3-dihydro-[1,4,3]oxathiazine,2,3-dihydro-[1,4,2]oxathiazine, 4,5-dihydropyridine,1,6-dihydropyridine, 5,6-dihydropyridine, 2H-pyran, 2H-thiin,3,6-dihydropyridine, 2,3-dihydropyridazine, 2,5-dihydropyridazine,4,5-dihydropyridazine, 1,2-dihydropyridazine, 2,3-dihydropyrimidine,2,5-dihydropyrimidine, 5,6-dihydropyrimidine, 3,6-dihydropyrimidine,4,5-dihydropyrazine, 5,6-dihydropyrazine, 3,6-dihydropyrazine,4,5-dihydropyrazine, 1,4-dihydropyrazine, 1,4-dithiin, 1,4-dioxin,2H-1,2-oxazine, 6H-1,2-oxazine, 4H-1,2-oxazine, 2H-1,3-oxazine,4H-1,3-oxazine, 6H-1,3-oxazine, 2H-1,4-oxazine, 4H-1,4-oxazine,2H-1,3-thiazine, 2H-1,4-thiazine, 4H-1,2-thiazine, 6RH-1,3-thiazine,4H-1,4-thiazine, 2H-1,2-thiazine, 6H-1,2-thiazine, 1,4-oxathiin,2H,5H-1,2,3-triazine, 1H,4H-1,2,3-triazine, 4,5-dihydro-1,2,3-triazine,1H,6H-1,2,3-triazine, 1,2-dihydro-1,2,3-triazine,2,3-dihydro-1,2,4-triazine, 3H,6H-1,2,4-triazine, 1H,6H-1,2,4-triazine,3,4-dihydro-1,2,4-triazine, 1H,4H-1,2,4-triazine,5,6-dihydro-1,2,4-triazine, 4,5-dihydro-1,2,4-triazine,2H,5H-1,2,4-triazine, 1,2-dihydro-1,2,4-triazine, 1H,4H-1,3,5-triazine,1,2-dihydro-1,3,5-triazine, 1,4,2-dithiazine, 1,4,2-dioxazine,2H-1,3,4-oxadiazine, 2H-1,3,5-oxadiazine, 6H-1,2,5-oxadiazine,4H-1,3,4-oxadiazine, 4H-1,3,5-oxadiazine, 4H-1,2,5-oxadiazine,2H-1,3,5-thiadiazine, 6H-1,2,5-thiadiazine, 4H-1,3,4-thiadiazine,4H-1,3,5-thiadiazine, 4H-1,2,5-thiadiazine, 2H-1,3,4-thiadiazine,6H-1,3,4-thiadiazine, 6H-1,3,4-oxadiazine and 1,4,2-oxathiazine and anybicyclic derivative of any of the above rings containing avicinally-fused phenyl, pyridine or pyrimidine, wherein the carbon atomsof the ring and bicyclic derivative are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring and bicyclic derivative are substitutedby 0, 1, 2, 3 or 4 substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl,halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), , —SR^(e),—S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f).—NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h),—NR^(h)C₂₋₆alkylNR^(a)R^(f).—NR^(a)C₂₋₆alkylNR^(a)R^(h),—NR^(h)C₂₋₆alkylOR^(f) and —NR^(a)C₂₋₆alkylOR^(h); and the ring andbicyclic derivative may be additionally substuted by C₁₋₄alkylsubstituted by 1, 2 or 3 substituents selected from halo, cyano, nitro,—C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),—OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h),—OC₂₋₆alkylOR^(h)—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(h),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

Embodiment A: In another embodiment, in conjunction with any one of theabove and below embodiments, R¹ is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 0, 1, 2 or 3 atomsselected from N, O and S, so long as the combination of O and S atoms isnot greater than 2, wherein the carbon atoms of the ring are substitutedby 0, 1 or 2 oxo or thioxo groups, wherein the ring is substituted by 0,1, 2, 3 or 4 substituents selected from C₁₋₈alkyl, halo, C₁₋₄haloalkyl,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —C(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a) ,—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 saturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groupsselected from R^(e), halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 C₁₋₄alkyl groups substituted by 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(d), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(h),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R⁴ is a ring selected from thiophene, pyrrole,1,3-oxazole, 1,3-thiazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole,1,2,3-oxadiazole, 1,2,3-thiadiazole, 1H-1,2,3-triazole, isothiazole,1,2,4-oxadiazole, 1,2,4-thiadiazole, 1,2,3,4-oxatriazole,1,2,3,4-thiatriazole, 1H-1,2,3,4-tetraazole, 1,2,3,5-oxatriazole,1,2,3,5-thiatriazole, furan, imidazol-1-yl, imidazol-4-yl,1,2,4-triazol-4-yl, 1,2,4-triazol-5-yl, isoxazol-3-yl, isoxazol-5-yl,thiolane, pyrrolidine, tetrahydrofuran, 4,5-dihydrothiophene,2-pyrroline, 4,5-dihydrofuran, pyridazine, pyrimidine, pyrazine,1,2,3-triazine, 1,2,4-triazine, 1,2,4-triazine, 1,3,5-triazine,pyridine, 2H-3,4,5,6-tetrahydropyran, thiane, 1,2-diazaperhydroine,1,3-diazaperhydroine, piperazine, 1,3-oxazaperhydroine, morpholine,1,3-thiazaperhydroine, 1,4-thiazaperhydroine, piperidine,2H-3,4-dihydropyran, 2,3-dihydro-4H-thiin, 1,4,5,6-tetrahydropyridine,2H-5,6-dihydropyran, 2,3-dihydro-6H-thiin, 1,2,5,6-tetrahydropyridine,3,4,5,6-tetrahydropyridine, 4H-pyran, 4H-thiin, 1,4-dihydropyridine,1,4-dithiane, 1,4-dioxane, 1,4-oxathiane, 1,2-oxazolidine,1,2-thiazolidine, pyrazolidine, 1,3-oxazolidine, 1,3-thiazolidine,imidazolidine, 1,2,4-oxadiazolidine, 1,3,4-oxadiazolidine,1,2,4-thiadiazolidine, 1,3,4-thiadiazolidine, 1,2,4-triazolidine,2-imidazoline, 3-imidazoline, 2-pyrazoline, 4-imidazoline,2,3-dihydroisothiazole, 4,5-dihydroisoxazole, 4,5-dihydroisothiazole,2,5-dihydroisoxazole, 2,5-dihydroisothiazole, 2,3-dihydroisoxazole,4,5-dihydrooxazole, 2,3-dihydrooxazole, 2,5-dihydrooxazole,4,5-dihydrothiazole, 2,3-dihydrothiazole,, 2,5-dihydrothiazole,1,3,4-oxathiazolidine, 1,4,2-oxathiazolidine,2,3-dihydro-1H-[1,2,3]triazole, 2,5-dihydro-1H-[1,2,3]triazole,4,5-dihydro-1H-[1,2,3]triazole, 2,3-dihydro-1H-[1,2,4]triazole,4,5-dihydro-1H-[1 ,2,4]triazole, 2,3-dihydro-[1,2,4]oxadiazole,2,5-dihydro-[1,2,4]oxadiazole, 4,5-dihydro-[1,2,4]thiadiazole,2,3-dihydro-[1,2,4] thidiazole, 2,5-dihydro-[1,2,4] thiadiazole,4,5-dihydro-[1,2,4] thiadiazole, 2,5-dihydro-[1,2,4]oxadiazole,2,3-dihydro-[1,2,4]oxadiazole, 4,5-dihydro-[1,2,4]oxadiazole,2,5-dihydro-[1,2,4]thiadiazole, 2,3-dihydro-[1,2,4] thiadiazole,4,5-dihydro-[1,2,4] thiadiazole, 2,3-dihydro-[1,3,4]oxadiazole,2,3-dihydro-[1,3,4]thiadiazole, [1,4,2]oxathiazole, [1,3,4]oxathiazole,1,3,5-triazaperhydroine, 1,2,4-triazaperhydroine,1,4,2-dithiazaperhydroine, 1,4,2-dioxazaperhydroine,1,3,5-oxadiazaperhydroine, 1,2,5-oxadiazaperhydroine,1,3,4-thiadiazaperhydroine, 1,3,5-thiadiazaperhydroine,1,2,5-thiadiazaperhydroine, 1,3,4-oxadiazaperhydroine,1,4,3-oxathiazaperhydroine, 1,4,2-oxathiazaperhydroine,1,4,5,6-tetrahydropyridazine, 1,2,3,4-tetrahydropyridazine,1,2,3,6-tetrahydropyridazine, 1,2,5,6-tetrahydropyrimidine,1,2,3,4-tetrahydropyrimidine, 1,4,5,6-tetrahydropyrimidine,1,2,3,6-tetrahydropyrazine, 1,2,3,4-tetrahydropyrazine,5,6-dihydro-4H-[1,2]oxazine, 5,6-dihydro-2H-[1,2]oxazine,3,6-dihydro-2H-[1,2]oxazine, 3,4-dihydro-2H-[1,2]oxazine,5,6-dihydro-4H-[1,2]thiazine, 5,6-dihydro-2H-[1,2] thiazine,3,6-dihydro-2H-[1,2] thiazine, 3,4-dihydro-2H-[1,2] thiazine,5,6-dihydro-2H-[1,3]oxazine, 5,6-dihydro-4H-[1,3]oxazine,3,6-dihydro-2H-[1,3]oxazine, 3,4-dihydro-2H-[1,3]oxazine,3,6-dihydro-2H-[1,4]oxazine, 3,4-dihydro-2H-[1,4]oxazine,5,6-dihydro-2H-[1,3]thiazine, 5,6-dihydro-4H-[1,3]thiazine,3,6-dihydro-2H-[1,3]thiazine, 3,4-dihydro-2H-[1,3]thiazine,3,6-dihydro-2H-[1,4]thiazine, 3,4-dihydro-2H-[1,4]thiazine,1,2,3,6-tetrahydro-[1,2,4]triazine, 1,2,3,4-tetrahydro-[1,2,4]triazine,1,2,3,4-tetrahydro-[1,3,5]triazine, 2,3,4,5-tetrahydro-[1,2,4]triazine,1,4,5,6-tetrahydro-[1,2,4]triazine, 5,6-dihydro-[1,4,2]dioxazine,5,6-dihydro-[1,4,2]dioxazine, 5,6-dihydro-[1,4,2]dithiazine,2,3-dihydro-[1,4,2]dioxazine, 3,4-dihydro-2H-[1,3,4]oxadiazine,3,6-dihydro-2H-[1,3,4]oxadiazine, 3,4-dihydro-2H-[1,3,5]oxadiazine,3,6-dihydro-2H-[1,3,5]oxadiazine, 5,6-dihydro-2H-[1,2,5]oxadiazine,5,6-dihydro-4H-[1,2,5]oxadiazine, 3,4-dihydro-2H-[1,3,4]thiadiazine,3,6-dihydro-2H-[1,3,4]thiadiazine, 3,4-dihydro-2H-[1,3,5]thiadiazine,3,6-dihydro-2H-[1,3,5]thiadiazine, 5,6-dihydro-2H-[1,2,5]thiadiazine,5,6-dihydro-4H-[1,2,5]thiadiazine, 5,6-dihydro-2H-[1,2,3]oxadiazine,3,6-dihydro-2H-[1,2,5]oxadiazine, 5,6-dihydro-4H-[1,3,4]oxadiazine,3,4-dihydro-2H-[1,2,5]oxadiazine, 5,6-dihydro-2H-[1,2,3]thiadiazine,3,6-dihydro-2H-[1,2,5]thiadiazine, 5,6-dihydro-4H-[1,3,4]thiadiazine,3,4-dihydro-2H-[1,2,5]thiadiazine, 5,6-dihydro-[1,4,3]oxathiazine,5,6-dihydro-[1,4,2]oxathiazine, 2,3-dihydro-[1,4,3]oxathiazine,2,3-dihydro-[1,4,2]oxathiazine, 4,5-dihydropyridine,1,6-dihydropyridine, 5,6-dihydropyridine, 2H-pyran, 2H-thiin,3,6-dihydropyridine, 2,3-dihydropyridazine, 2,5-dihydropyridazine,4,5-dihydropyridazine, 1,2-dihydropyridazine, 2,3-dihydropyrimidine,2,5-dihydropyrimidine, 5,6-dihydropyrimidine, 3,6-dihydropyrimidine,4,5-dihydropyrazine, 5,6-dihydropyrazine, 3,6-dihydropyrazine,4,5-dihydropyrazine, 1,4-dihydropyrazine, 1,4-dithiin, 1,4-dioxin,2H-1,2-oxazine, 6H-1,2-oxazine, 4H-1,2-oxazine, 2H-1,3-oxazine,4H-1,3-oxazine, 6H-1,3-oxazine, 2H-1,4-oxazine, 4H-1,4-oxazine,2H-1,3-thiazine, 2H-1,4-thiazine, 4H-1,2-thiazine, 6H-1,3-thiazine,4H-1,4-thiazine, 2H-1,2-thiazine, 6H-1,2-thiazine, 1,4-oxathiin,2H,5H-1,2,3-triazine, 1H,4H-1,2,3-triazine, 4,5-dihydro-1,2,3-triazine,1H,6H-1,2,3-triazine, 1,2-dihydro-1,2,3-triazine,2,3-dihydro-1,2,4-triazine, 3H,6H-1,2,4-triazine, 1H,6H-1,2,4-triazine,3,4-dihydro-1,2,4-triazine, 1H,4H-1,2,4-triazine,5,6-dihydro-1,2,4-triazine, 4,5-dihydro-1,2,4-triazine,2H,5H-1,2,4-triazine, 1,2-dihydro-1,2,4-triazine, 1H,4H-1,3,5-triazine,1,2-dihydro-1,3,5-triazine, 1,4,2-dithiazine, 1,4,2-dioxazine,2H-1,3,4-oxadiazine, 2H-1,3,5-oxadiazine, 6H-1,2,5-oxadiazine,4H-1,3,4-oxadiazine, 4H-1,3,5-oxadiazine, 4H-1,2,5-oxadiazine,2H-1,3,5-thiadiazine, 6H-1,2,5-thiadiazine, 4H-1,3,4-thiadiazine,4H-1,3,5-thiadiazine, 4H-1,2,5-thiadiazine, 2H-1,3,4-thiadiazine,6H-1,3,4-thiadiazine, 6H-1,3,4-oxadiazine, 1,4,2-oxathiazine and anybicyclic derivative of any of the above rings containing avicinally-fused phenyl, pyridine or pyrimidine, wherein the carbon atomsof the ring and bicyclic derivative are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring and bicyclic derivative are substitutedby 0, 1, 2, 3 or 4 substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl,halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R³)C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h)—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring and bicyclic derivative may beadditionally substuted by C₁₋₄alkyl substituted by 1, 2 or 3substituents selected from halo, cyano, nitro, —C(═O)R^(e),—C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f).—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

Embodiment B: In another embodiment, in conjunction with any one of theabove and below embodiments, R⁴ is a saturated, partially-saturated orunsaturated 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 0, 1, 2, 3 or 4atoms selected from N, O and S, so long as the combination of O and Satoms is not greater than 2, wherein the carbon atoms of the ring aresubstituted by 0, 1 or 2 oxo or thioxo groups, wherein the ring issubstituted by 0, 1, 2, 3 or 4 substituents selected from C₁₋₈alkyl,C₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂ NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, X is C(R²); Y is N; and Z is N.

Embodiment C: In another embodiment, in conjunction with any one of theabove and below embodiments, R⁴ is a saturated, partially-saturated orunsaturated 8-, 9-, 10- or 11-membered vicinally-fused bicyclic ringcontaining 1 N atom and 0, 1, 2, or 3 additional atoms selected from N,O and S, so long as the combination of O and S atoms is not greater than2, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxoor thioxo groups, wherein the ring is substituted by 0, 1, 2, 3 or 4substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl, halo, cyano, nitro,—C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),—OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R², —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, X is N; Y is N; and Z is C(R^(d)).

Embodiment D: In another embodiment, in conjunction with any one of theabove and below embodiments, R² is, independently, in each instance,selected from H, C₁₋₈alkyl, halo, C₁₋₄haloalkyl, cyano, nitro,—C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),—OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R, —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); or R² is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 1, 2, 3 or 4 atomsselected from N, O and S, so long as the combination of O and S atoms isnot greater than 2, wherein the carbon atoms of the ring are substitutedby 0, 1 or 2 oxo or thioxo groups, wherein the ring is substituted by 0,1, 2 or 3 groups selected from R^(e), halo, cyano, nitro, —C(═O)R^(e),—C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), -s (═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂ NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); or R² is phenyl or phenyl substituted by 1, 2 or3 groups selected from R^(e), cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f).—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R³, —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆akylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); wherein the substituted phenyl is additionallysubstituted by 0, 1 or 2 halo atoms; or R² is C₁₋₄alkyl substituted by0, 1, 2 or 3 groups selected from C₁₋₄haloalkyl, halo, cyano, nitro,—C(═O)R^(e), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f),I—N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆akylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

Embodiment E: In another embodiment, in conjunction with any one of theabove and below embodiments, R⁴ is a saturated, partially-saturated orunsaturated 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 0, 1, 2, 3 or 4atoms selected from N, O and S, so long as the combination of O and Satoms is not greater than 2, wherein the carbon atoms of the ring aresubstituted by 0, 1 or 2 oxo or thioxo groups, wherein the ring issubstituted by 0, 1, 2, 3 or 4 substituents selected from C₁₋₈alkyl,C₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R³, —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂ NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

Embodiment F: In another embodiment, in conjunction with any one of theabove and below embodiments, R² is, independently, in each instance,selected from H, C₂₋₈alkyl, halo, C₁₋₄haloalkyl, cyano, nitro,—C(═O)R^(e), ,C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f).—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h) or R² is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 1, 2, 3 or 4 atomsselected from N, O and S, so long as the combination of O and S atoms isnot greater than 2, wherein the carbon atoms of the ring are substitutedby 0, 1 or 2 oxo or thioxo groups, wherein the ring is substituted by 0,1, 2 or 3 groups selected from R^(e), halo, cyano, nitro, —C(═O)R^(e),—C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂ NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h) or R² is phenyl or phenyl substituted by 1, 2 or3 groups selected from cyano, nitro, —C(═O)R^(e),—C(═O)OR^(f),C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —C(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆akylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); wherein the substituted phenyl is additionallysubstituted by 0, 1 or 2 substituents selected from R^(e) and halo; orR² is C₁₋₄alkyl substituted by 0, 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), s(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f).—NR^(a)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

Embodiment G: In another embodiment, in conjunction with any one of theabove and below embodiments, R⁴ is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 1, 2, 3 or 4 atomsselected from N, O and S, so long as the combination of O and S atoms isnot greater than 2, wherein the carbon atoms of the ring are substitutedby 0, 1 or 2 oxo or thioxo groups, wherein the ring is substituted by 0,1, 2, 3 or 4 substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl, halo,nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(q)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); or R⁴ is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic carbocyclic ring, wherein the ringis substituted by 0, 1 or 2 oxo or thioxo groups, and wherein the ringis additionally substituted by 0, 1, 2, 3 or 4 substituents selectedfrom C₁₋₈alkyl, halo, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R²f, —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O),NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and wherein when the carbocyclic ring is otherthan unsubstituted phenyl it may be additionally substituted by 0, 1 or2 C₁₋₄haloalkyl groups; wherein R⁴ is not pyrazole or indazole or anypartially saturated or substituted version thereof.

In another embodiment, in conjunction with any one of the above andbelow embodiments, R⁴ is a saturated, partially-saturated or unsaturated5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-memberedvicinally-fused bicyclic ring containing 1, 2, 3 or 4 atoms selectedfrom N, O and S, so long as the combination of O and S atoms is notgreater than 2, and wherein the ring does not contain any adjacent Natoms, wherein the carbon atoms of the ring are substituted by 0, 1 or 2oxo or thioxo groups, wherein the ring is substituted by 0, 1, 2, 3 or 4substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl, halo, nitro,—C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),—OR^(f), —OC(═O)R^(e), —C(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); or R⁴ is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic carbocyclic ring, wherein the ringis substituted by 0, 1 or 2 oxo or thioxo groups, and wherein the ringis additionally substituted by 0, 1, 2, 3 or 4 substituents selectedfrom C₁₋₈alkyl, halo, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR²,—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e).—S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and wherein when the carbocyclic ring is otherthan unsubstituted phenyl it may be additionally substituted by 0, 1 or2 C₁₋₄haloalkyl groups.

In another embodiment, in conjunction with any one of the above andbelow embodiments, X is N; Y is C(R³); and Z is C(R^(d)).

Embodiment H: In another embodiment, in conjunction with any one of theabove and below embodiments, R¹ is a carbon-linked saturated,partially-saturated or unsaturated 5-, 6- or 7-membered monocyclic or6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fused bicyclic ringcontaining 0, 1, 2, 3 or 4 atoms selected from N, O and S, so long asthe combination of O and S atoms is not greater than 2, wherein thecarbon atoms of the ring are substituted by 0, 1 or 2 oxo or thioxogroups, wherein the ring is substituted by 0, 1, 2, 3 or 4 substituentsselected from C₁₋₈alkyl, halo, C₁₋₄haloalkyl, cyano, nitro, —C(═O)R^(e),—C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆akylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 saturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groupsselected from R^(e), halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—C(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —C(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 C₁₋₄alkyl groups substituted by 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)NR^(a)R^(f),—C(═NR)NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f),SR^(e), , —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂ NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)R^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N a)C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); wherein R¹ is not tetrazole.

Embodiment I: In another embodiment, in conjunction with any one of theabove and below embodiments, R² is, independently, in each instance,selected from H, C₁₋₈alkyl, halo, C₁₋₄haloalkyl, nitro, —C(═O)R^(e),—C(═O)OR^(f), —C(═O)N(H)R^(f), —C(═NR^(a))NR^(a), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f). —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); or R² is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 0, 1, 2, 3 or 4atoms selected from N, O and S, so long as the combination of O and Satoms is not greater than 2, wherein the carbon atoms of the ring aresubstituted by 0, 1 or 2 oxo or thioxo groups, wherein the ring issubstituted by 0, 1, 2 or 3 groups selected from R^(e), halo, cyano,nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f).—OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(a)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); or R² is C₁₋₄alkyl substituted by 0, 1, 2 or 3groups selected from C₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f).—N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆akylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h);

In another embodiment, in conjunction with any one of the above andbelow embodiments, R³ is, independently, in each instance, H, halo,—NH₂, —NHC₁₋₃alkyl, —N(C₁₋₃alkyl)C₁₋₃alkyl, or C₁₋₃alkyl;

Embodiment J: In another embodiment, in conjunction with any one of theabove and below embodiments, R⁴ is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 1, 2, 3 or 4 atomsselected from N, O and S, so long as the combination of O and S atoms isnot greater than 2, and no N atom is adjacent to another N atom, whereinthe carbon atoms of the ring are substituted by 0, 1 or 2 oxo or thioxogroups, wherein the ring is substituted by 0, 1, 2, 3 or 4 substituentsselected from C₁₋₅alkyl, C₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e),—C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂ NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a),R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h) or R⁴ is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic carbocyclic ring substituted by 0,1 or 2 oxo or thioxo groups, and additionally substituted by 0, 1, 2, 3or 4 substituents selected from C₁₋₅alkyl, C₁₋₄haloalkyl, halo, cyano,—C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),—OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R²,—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a)R^(a))NR^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R¹ is a saturated, partially-saturated or unsaturated9-, 10- or 11-membered vicinally-fused bicyclic ring containing 0, 1, 2or 3 atoms selected from N, O and S, so long as the combination of O andS atoms is not greater than 2, wherein the carbon atoms of the ring aresubstituted by 0, 1 or 2 oxo or thioxo groups, wherein the ring issubstituted by 0, 1, 2, 3 or 4 substituents selected from C₁₋₈alkyl,halo, C₁₋₄haloalkyl, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a) )NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), , —S(═O)R^(e), —S(═O)₂R^(e), ,—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O )₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(h), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 saturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groupsselected from R^(e), halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), ,S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 C₁₋₄alkyl groups substituted by 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R¹ is a saturated, partially-saturated or unsaturated9-, 10- or 11-membered vicinally-fused bicyclic ring containing 1, 2 or3 atoms selected from N, O and S, so long as the combination of O and Satoms is not greater than 2, wherein the carbon atoms of the ring aresubstituted by 0, 1 or 2 oxo or thioxo groups, wherein the ring issubstituted by 0, 1, 2, 3 or 4 substituents selected from C₁₋₈alkyl,halo, C₁₋₄haloalkyl, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(e), —OC(═O)R^(e),—C(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆akylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 saturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groupsselected from R^(e), halo, cyano, nitro, —C(═O)R^(e),—C(═O)OR^(f),C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —S R^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f).—C(═O)R^(h),—C(═O)OR^(h)C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 C₁₋₄alkyl groups substituted by 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(e), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R¹ is a saturated, partially-saturated or unsaturated9-, 10- or 11-membered vicinally-fused bicyclic ring containing 1, 2 or3 atoms selected from N, O and S, so long as the combination of O and Satoms is not greater than 2, wherein the carbon atoms of the ring aresubstituted by 0, 1 or 2 oxo or thioxo groups, wherein the ring issubstituted by 1, 2, 3 or 4 substituents selected from C₁₋₈alkyl, halo,C₁₋₄haloalkyl, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —C(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(f), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f).—N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 saturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groupsselected from R^(e), halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—C(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(h),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 C₁₋₄alkyl groups substituted by 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)NR^(a)R^(f),—C(═NR)NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(h), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(h), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(h), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R¹ is a saturated, partially-saturated or unsaturated5-, 6- or 7-membered monocyclic ring containing 0, 1, 2 or 3 atomsselected from N, O and S, so long as the combination of O and S atoms isnot greater than 2, wherein the carbon atoms of the ring are substitutedby 0, 1 or 2 oxo or thioxo groups, wherein the ring is substituted by 0,1, 2, 3 or 4 substituents selected from C₁₋₈alkyl, halo, C₁₋₄haloalkyl,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 saturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groupsselected from R^(e), halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 C₁₋₄alkyl groups substituted by 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

Embodiment K: In another embodiment, in conjunction with any one of theabove and below embodiments, R¹ is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic ring containing 1, 2 or 3atoms selected from N, O and S, so long as the combination of O and Satoms is not greater than 2, wherein the carbon atoms of the ring aresubstituted by 0, 1 or 2 oxo or thioxo groups, wherein the ring issubstituted by 0, 1, 2, 3 or 4 substituents selected from C₁₋₈alkyl,halo, C₁₋₄haloalkyl, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R²)S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h),—N(R^(h))S(═O)₂NR^(a)R^(f), —N(R^(a))S(═O)₂NR^(a)R^(h),—NR^(h)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(h); and the ringis additionally substituted by 0 or 1 saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 0, 1, 2, 3 or 4atoms selected from N, O and S, so long as the combination of O and Satoms is not greater than 2, wherein the carbon atoms of the ring aresubstituted by 0, 1 or 2 oxo or thioxo groups, wherein the ring issubstituted by 0, 1, 2 or 3 groups selected from R^(e), halo, cyano,nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —C(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(e), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 C₁₋₄alkyl groups substituted by 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(e), —OC(═O)R^(e), —C(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(h),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

Embodiment L: In another embodiment, in conjunction with any one of theabove and below embodiments, R¹ is phenyl substituted by 1, 2, 3 or 4substituents selected from C₁₋₈alkyl, halo, C₁₋₄haloalkyl, cyano, nitro,—C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),—OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f).—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —C(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the phenyl is additionally substituted by 0or 1 saturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groupsselected from R^(e), halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(e), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the phenyl is additionally substituted by 0or 1 C₁₋₄alkyl groups substituted by 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(e), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),,NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R¹ is phenyl substituted by 0, 1, 2, 3 or 4substituents selected from C₁₋₈alkyl, halo, C₁₋₄haloalkyl, cyano, nitro,—C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),—OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the phenyl is additionally substituted by asaturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groupsselected from R^(e), halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the phenyl is —NR^(a)C₂₋₆alkylNR^(a)R^(h),—NR^(h)C₂₋₆alkylOR^(f) and —NR^(a)C₂₋₆alkylOR^(h); and the phenyl isadditionally substituted by 0 or 1 C₁₋₄alkyl groups substituted by 1, 2or 3 groups selected from C₁₋₄haloalkyl, halo, cyano, nitro,—C(═O)R^(e), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f))—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R¹ is phenyl substituted by 0, 1, 2, 3 or 4substituents selected from C₁₋₈alkyl, halo, C₁₋₄haloalkyl, cyano, nitro,—C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),—OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R²,—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the phenyl is additionally substituted by 0or 1 saturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groupsselected from R^(e), halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f).—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)R^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the phenyl is additionally substituted by aC₁₋₄alkyl groups substituted by 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R¹ is phenyl substituted in the para position byeither C₃₋₅alkyl or C₁₋₂haloalkyl, and the phenyl is additionallysubstituted by 0, 1, or 2 substituents selected from C₁₋₈alkyl, halo,C₁₋₄haloalkyl, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R², —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the phenyl is additionally substituted by 0or 1 saturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groupsselected from R^(e), halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h),—NR^(h)C₂₋₆alkylNR^(a)R^(f).—NR^(a)C₂₋₆alkylNR^(a)R^(h),—NR^(h)C₂₋₆alkylOR^(f) and —NR^(a)C₂₋₆alkylOR^(h); and the phenyl isadditionally substituted by 0 or 1 C₁₋₄alkyl groups substituted by 1, 2or 3 groups selected from C₁₋₄haloalkyl, halo, cyano, nitro,—C(═O)R^(e), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(e),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R¹ is phenyl substituted in the para position byeither C₃₋₅alkyl or C₁₋₂haloalkyl.

In another embodiment, in conjunction with any one of the above andbelow embodiments, R¹ is 4-tert-butylphenyl.

In another embodiment, in conjunction with any one of the above andbelow embodiments, R¹ is 4-trifluoromethylphenyl.

Embodiment M: In another embodiment, in conjunction with any one of theabove and below embodiments, R² is H.

Embodiment N: In another embodiment, in conjunction with any one of theabove and below embodiments, R² is, independently, in each instance,selected from C₁₋₈alkyl, halo, C₁₋₄haloalkyl, cyano, nitro, —C(═O)R^(e),—C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R²,—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

Embodiment O: In another embodiment, in conjunction with any one of theabove and below embodiments, R² is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 0, 1, 2, 3 or 4atoms selected from N, O and S, so long as the combination of O and Satoms is not greater than 2, wherein the carbon atoms of the ring aresubstituted by 0, 1 or 2 oxo or thioxo groups, wherein the ring issubstituted by 0, 1, 2 or 3 groups selected from R^(e), halo, cyano,nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R² is C₁₋₄alkyl substituted by 0, 1, 2 or 3 groupsselected from C₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R² is C₁₋₄alkyl substituted by 1, 2 or 3 groupsselected from C₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—C(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e). N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R³ is H.

In another embodiment, in conjunction with any one of the above andbelow embodiments, R³ is, independently, in each instance, halo, —NH₂,—NHC₁₋₃alkyl, —N(C₁₋₃alkyl)C₁₋₃alkyl, or C₁₋₃alkyl.

Embodiment P: In another embodiment, in conjunction with any one of theabove and below embodiments, R⁴ is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 1, 2, 3 or 4 atomsselected from N, O and S, so long as the combination of O and S atoms isnot greater than 2, wherein the carbon atoms of the ring are substitutedby 0, 1 or 2 oxo or thioxo groups, wherein the ring is substituted by 0,1, 2, 3 or 4 substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl, halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)NR^(h)C₂₋₆akylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f).—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); wherein R⁴ is not pyrrolidine or pyrazole.

In another embodiment, in conjunction with any one of the above andbelow embodiments, R⁴ is a saturated, partially-saturated or unsaturated5-, 6- or 7-membered monocyclic ring containing 1, 2, 3 or 4 atomsselected from N, O and S, so long as the combination of O and S atoms isnot greater than 2, wherein the carbon atoms of the ring are substitutedby 0, 1 or 2 oxo or thioxo groups, wherein the ring is substituted by 0,1, 2, 3 or 4 substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl, halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f).—OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂,NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); wherein R⁴ is not pyrrolidine or pyrazole.

In another embodiment, in conjunction with any one of the above andbelow embodiments, R⁴ is a saturated, partially-saturated or unsaturated6- or 7-membered monocyclic ring containing 1, 2, 3 or 4 atoms selectedfrom N, O and S, so long as the combination of O and S atoms is notgreater than 2, wherein the carbon atoms of the ring are substituted by0, 1 or 2 oxo or thioxo groups, wherein the ring is substituted by 0, 1,2, 3 or 4 substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl, halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₁₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R⁴ is a saturated, partially-saturated or unsaturated5-, 6- or 7-membered monocyclic ring containing 1, 2, 3 or 4 atomsselected from N, O and S, so long as the combination of O and S atoms isnot greater than 2, wherein the carbon atoms of the ring are substitutedby 0, 1 or 2 oxo or thioxo groups, wherein the ring is substituted by 1,2, 3 or 4 substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl, halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(e), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(e), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(d),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

Embodiment Q: In another embodiment, in conjunction with any one of theabove and below embodiments, R⁴ is a saturated, partially-saturated orunsaturated 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fused bicyclicring containing 1, 2, 3 or 4 atoms selected from N, O and S, so long asthe combination of O and S atoms is not greater than 2, wherein thecarbon atoms of the ring are substituted by 0, 1 or 2 oxo or thioxogroups, wherein the ring is substituted by 0, 1, 2, 3 or 4 substituentsselected from C₁₋₈alkyl, C₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e),—C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(e), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a) ,—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R⁴ is a partially-saturated or unsaturated 9-, 10- or11-membered vicinally-fused bicyclic ring containing 1, 2, 3 or 4 atomsselected from N, O and S, so long as the combination of O and S atoms isnot greater than 2, wherein at least one of the bicyclic rings isaromatic, and wherein the carbon atoms of the ring are substituted by 0,1 or 2 oxo or thioxo groups, wherein the ring is substituted by 0, 1, 2,3 or 4 substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl, halo, cyano,nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R²,—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f).—S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

Embodiment R: In another embodiment, in conjunction with any one of theabove and below embodiments, R⁴ is a partially-saturated or unsaturated9-, 10- or 11-membered vicinally-fused bicyclic ring containing 1, 2, 3or 4 atoms selected from N, O and S, so long as the combination of O andS atoms is not greater than 2,, wherein at least one of the bicyclicrings is aromatic, and wherein the carbon atoms of the ring aresubstituted by 0, 1 or 2 oxo or thioxo groups, wherein the ring issubstituted by 1, 2, 3 or 4 substituents selected from C₁₋₈alkyl,C₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R³)C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂ NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))Na R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R⁴ is naphthyl substituted by 0, 1, 2, 3 or 4substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl, halo, cyano, nitro,—C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),—OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the naphthyl may be additionally substutedby C₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

In another embodiment, in conjunction with any one of the above andbelow embodiments, R³⁴ is phenyl substituted by 0, 1, 2, 3 or 4substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl, halo, cyano, nitro,—C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),—OR^(f), —OC(═O)R^(e), —C(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f).—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(h),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the phenyl may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—C(═O)NR^(a)R^(f).—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂ NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R², —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).

The following tables represent some specific embodiments selected fromthe larger list of embodiments described above. Where X is C(R²) and Yis N and Z is H: Emb. # R¹ R² R⁴ 1001 A M B 1002 A M P 1003 A M Q 1004 AM R 1005 A N B 1006 A N P 1007 A N Q 1008 A N R 1009 A O B 1010 A O P1011 A O Q 1012 A O R 1013 K M B 1014 K N B 1015 K O B 1016 L M B 1017 LN B 1018 L O B

Where X is H and Y is N and Z is C(R^(d)): Emb. # R¹ R² R⁴ 1019 A M B1020 A M P 1021 A M Q 1022 A M R 1023 A N B 1024 A N P 1025 A N Q 1026 AN R 1027 A O B 1028 A O P 1029 A O Q 1030 A O R 1031 K M B 1032 K N B1033 K O B 1034 L M B 1035 L N B 1036 L O B

Where X is C(R²) and Y is N and Z is N: Emb. # R¹ R² R⁴ 1037 K C P 1038L C P 1039 K C Q 1040 L C Q 1041 K C R 1042 L C R

Where X is N and Y is N and Z is C(R^(d)): Emb. # R¹ R² R⁴ 1043 K D P1044 L D P 1045 K D Q 1046 L D Q 1047 K D R 1048 L D R 1049 K D E 1050 LD E 1051 K M E 1052 L M E 1053 K N E 1054 L N E 1055 K O E 1056 L O E

Where X is N and Y is C(R³) and Z is C(R^(d)): Emb. # R¹ R² R⁴ 1071 H MJ 1072 H M P 1073 H M Q 1074 H M R 1075 H N J 1076 H N P 1077 H N Q 1078H N R 1079 H O J 1080 H O P 1081 H O Q 1082 H O R 1083 H I J 1084 H I P1085 H I Q 1086 H I R 1087 K I J 1088 L I J 1089 K M J 1090 K N J 1091 KO J 1092 L M J 1093 L N J 1094 L O J

Another aspect of the invention relates to a method of treating acute,inflammatory and neuropathic pain, dental pain, general headache,migraine, cluster headache, mixed-vascular and non-vascular syndromes,tension headache, general inflammation, arthritis, rheumatic diseases,osteoarthritis, inflammatory bowel disorders, inflammatory eyedisorders, inflammatory or unstable bladder disorders, psoriasis, skincomplaints with inflammatory components, chronic inflammatoryconditions, inflammatory pain and associated hyperalgesia and allodynia,neuropathic pain and associated hyperalgesia and allodynia, diabeticneuropathy pain, causalgia, sympathetically maintained pain,deafferentation syndromes, asthma, epithelial tissue damage ordysfunction, herpes simplex, disturbances of visceral motility atrespiratory, genitourinary, gastrointestinal or vascular regions,wounds, burns, allergic skin reactions, pruritus, vitiligo, generalgastrointestinal disorders, gastric ulceration, duodenal ulcers,diarrhea, gastric lesions induced by necrotising agents, hair growth,vasomotor or allergic rhinitis, bronchial disorders or bladderdisorders, comprising the step of administering a compound according toany of the above embodiments.

Another aspect of the invention relates to a pharmaceutical compositioncomprising a compound according to any of the above embodiments and apharmaceutically-acceptable diluent or carrier.

Another aspect of the invention relates to the use of a compoundaccording to any of the above embodiments as a medicament.

Another aspect of the invention relates to the use of a compoundaccording to any of the above embodiments in the manufacture of amedicament for the treatment of acute, inflammatory and neuropathicpain, dental pain, general headache, migraine, cluster headache,mixed-vascular and non-vascular syndromes, tension headache, generalinflammation, arthritis, rheumatic diseases, osteoarthritis,inflammatory bowel disorders, inflammatory eye disorders, inflammatoryor unstable bladder disorders, psoriasis, skin complaints withinflammatory components, chronic inflammatory conditions, inflammatorypain and associated hyperalgesia and allodynia, neuropathic pain andassociated hyperalgesia and allodynia, diabetic neuropathy pain,causalgia, sympathetically maintained pain, deafferentation syndromes,asthma, epithelial tissue damage or dysfunction, herpes simplex,disturbances of visceral motility at respiratory, genitourinary,gastrointestinal or vascular regions, wounds, burns, allergic skinreactions, pruritus, vitiligo, general gastrointestinal disorders,gastric ulceration, duodenal ulcers, diarrhea, gastric lesions inducedby necrotising agents, hair growth, vasomotor or allergic rhinitis,bronchial disorders or bladder disorders.

The compounds of this invention may have in general several asymmetriccenters and are typically depicted in the form of racemic mixtures. Thisinvention is intended to encompass racemic mixtures, partially racemicmixtures and separate enantiomers and diasteromers.

Unless otherwise specified, the following definitions apply to termsfound in the specification and claims:

“C_(α-β)alkyl” means an alkyl group comprising a minimum of α and amaximum of β carbon atoms in a branched, cyclical or linear relationshipor any combination of the three, wherein α and β represent integers. Thealkyl groups described in this section may also contain one or twodouble or triple bonds. Examples of C₁₋₆alkyl include, but are notlimited to the following:

“Benzo group”, alone or in combination, means the divalent radicalC₄H₄═, one representation of which is —CH═CH—CH═CH—, that when vicinallyattached to another ring forms a benzene-like ring—for exampletetrahydronaphthylene, indole and the like.

The terms “oxo” and “thioxo” represent the groups =0 (as in carbonyl)and ═S (as in thiocarbonyl), respectively.

“Halo” or “halogen” means a halogen atoms selected from F, Cl, Br and I.“C_(V-W)haloalkyl” means an alkyl group, as described above, wherein anynumber—at least one—of the hydrogen atoms attached to the alkyl chainare replaced by F, Cl, Br or I.

“Heterocycle” means a ring comprising at least one carbon atom and atleast one other atom selected from N, O and S. Examples of heterocyclesthat may be found in the claims include, but are not limited to, thefollowing:

“Available nitrogen atoms” are those nitrogen atoms that are part of aheterocycle and are joined by two single bonds (e.g. piperidine),leaving an external bond available for substitution by, for example, Hor CH₃.

“Pharmaceutically-acceptable salt” means a salt prepared by conventionalmeans, and are well known by those skilled in the art. The“pharmacologically acceptable salts” include basic salts of inorganicand organic acids, including but not limited to hydrochloric acid,hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid,ethanesulfonic acid, malic acid, acetic acid, oxalic acid, tartaricacid, citric acid, lactic acid, fumaric acid, succinic acid, maleicacid, salicylic acid, benzoic acid, phenylacetic acid, mandelic acid andthe like. When compounds of the invention include an acidic functionsuch as a carboxy group, then suitable pharmaceutically acceptablecation pairs for the carboxy group are well known to those skilled inthe art and include alkaline, alkaline earth, ammonium, quaternaryammonium cations and the like. For additional examples of“pharmacologically acceptable salts,” see infra and Berge et al., J.Pharm. Sci. 66:1 (1977).

“Saturated or unsaturated” includes substituents saturated withhydrogens, substituents completely unsaturated with hydrogens andsubstituents partially saturated with hydrogens.

“Leaving group” generally refers to groups readily displaceable by anucleophile, such as an amine, a thiol or an alcohol nucleophile. Suchleaving groups are well known in the art. Examples of such leavinggroups include, but are not limited to, N-hydroxysuccinimide,N-hydroxybenzotriazole, halides, triflates, tosylates and the like.Preferred leaving groups are indicated herein where appropriate.“Protecting group” generally refers to groups well known in the artwhich are used to prevent selected reactive groups, such as carboxy,amino, hydroxy, mercapto and the like, from undergoing undesiredreactions, such as nucleophilic, electrophilic, oxidation, reduction andthe like. Preferred protecting groups are indicated herein whereappropriate. Examples of amino protecting groups include, but are notlimited to, aralkyl, substituted aralkyl, cycloalkenylalkyl andsubstituted cycloalkenyl alkyl, allyl, substituted allyl, acyl,alkoxycarbonyl, aralkoxycarbonyl, silyl and the like. Examples ofaralkyl include, but are not limited to, benzyl, ortho-methylbenzyl,trityl and benzhydryl, which can be optionally substituted with halogen,alkyl, alkoxy, hydroxy, nitro, acylamino, acyl and the like, and salts,such as phosphonium and ammonium salts. Examples of aryl groups includephenyl, naphthyl, indanyl, anthracenyl, 9-(9-phenylfluorenyl),phenanthrenyl, durenyl and the like. Examples of cycloalkenylalkyl orsubstituted cycloalkylenylalkyl radicals, preferably have 6-10 carbonatoms, include, but are not limited to, cyclohexenyl methyl and thelike. Suitable acyl, alkoxycarbonyl and aralkoxycarbonyl groups includebenzyloxycarbonyl, t-butoxycarbonyl, iso-butoxycarbonyl, benzoyl,substituted benzoyl, butyryl, acetyl, trifluoroacetyl, trichloro acetyl,phthaloyl and the like. A mixture of protecting groups can be used toprotect the same amino group, such as a primary amino group can beprotected by both an aralkyl group and an aralkoxycarbonyl group. Aminoprotecting groups can also form a heterocyclic ring with the nitrogen towhich they are attached, for example, 1,2-bis(methylene)benzene,phthalimidyl, succinimidyl, maleimidyl and the like and where theseheterocyclic groups can further include adjoining aryl and cycloalkylrings. In addition, the heterocyclic groups can be mono-, di- ortri-substituted, such as nitrophthalimidyl. Amino groups may also beprotected against undesired reactions, such as oxidation, through theformation of an addition salt, such as hydrochloride, toluenesulfonicacid, trifluoroacetic acid and the like. Many of the amino protectinggroups are also suitable for protecting carboxy, hydroxy and mercaptogroups. For example, aralkyl groups. Alkyl groups are also suitablegroups for protecting hydroxy and mercapto groups, such as tert-butyl.

Silyl protecting groups are silicon atoms optionally substituted by oneor more alkyl, aryl and aralkyl groups. Suitable silyl protecting groupsinclude, but are not limited to, trimethylsilyl, triethylsilyl,triisopropylsilyl, tert-butyldimethylsilyl, dimethylphenylsilyl,1,2-bis(dimethylsilyl)benzene, 1,2-bis(dimethylsilyl)ethane anddiphenylmethylsilyl. Silylation of an amino groups provide mono- ordi-silylamino groups. Silylation of aminoalcohol compounds can lead to aN,N,O-trisilyl derivative. Removal of the silyl function from a silylether function is readily accomplished by treatment with, for example, ametal hydroxide or ammonium fluoride reagent, either as a discretereaction step or in situ during a reaction with the alcohol group.Suitable silylating agents are, for example, trimethylsilyl chloride,tert-butyl-dimethylsilyl chloride, phenyldimethylsilyl chloride,diphenylmethyl silyl chloride or their combination products withimidazole or DMF. Methods for silylation of amines and removal of silylprotecting groups are well known to those skilled in the art. Methods ofpreparation of these amine derivatives from corresponding amino acids,amino acid amides or amino acid esters are also well known to thoseskilled in the art of organic chemistry including amino acid/amino acidester or aminoalcohol chemistry.

Protecting groups are removed under conditions which will not affect theremaining portion of the molecule. These methods are well known in theart and include acid hydrolysis, hydrogenolysis and the like. Apreferred method involves removal of a protecting group, such as removalof a benzyloxycarbonyl group by hydrogenolysis utilizing palladium oncarbon in a suitable solvent system such as an alcohol, acetic acid, andthe like or mixtures thereof. A t-butoxycarbonyl protecting group can beremoved utilizing an inorganic or organic acid, such as HCl ortrifluoroacetic acid, in a suitable solvent system, such as dioxane ormethylene chloride. The resulting amino salt can readily be neutralizedto yield the free amine. Carboxy protecting group, such as methyl,ethyl, benzyl, tert-butyl, 4-methoxyphenylmethyl and the like, can beremoved under hydrolysis and hydrogenolysis conditions well known tothose skilled in the art.

It should be noted that compounds of the invention may contain groupsthat may exist in tautomeric forms, such as cyclic and acyclic amidineand guanidine groups, heteroatom substituted heteroaryl groups (Y′=O, S,NR), and the like, which are illustrated in the following examples:

and though one form is named, described, displayed and/or claimedherein, all the tautomeric forms are intended to be inherently includedin such name, description, display and/or claim.

Prodrugs of the compounds of this invention are also contemplated bythis invention. A prodrug is an active or inactive compound that ismodified chemically through in vivo physiological action, such ashydrolysis, metabolism and the like, into a compound of this inventionfollowing administration of the prodrug to a patient. The suitabilityand techniques involved in making and using prodrugs are well known bythose skilled in the art. For a general discussion of prodrugs involvingesters see Svensson and Tunek Drug Metabolism Reviews 165 (1988) andBundgaard Design of Prodrugs, Elsevier (1985). Examples of a maskedcarboxylate anion include a variety of esters, such as alkyl (forexample, methyl, ethyl), cycloalkyl (for example, cyclohexyl), aralkyl(for example, benzyl, p-methoxybenzyl), and alkylcarbonyloxyalkyl (forexample, pivaloyloxymethyl). Amines have been masked asarylcarbonyloxymethyl substituted derivatives which are cleaved byesterases in vivo releasing the free drug and formaldehyde (Bungaard J.Med. Chem. 2503 (1989)). Also, drugs containing an acidic NH group, suchas imidazole, imide, indole and the like, have been masked withN-acyloxymethyl groups (Bundgaard Design of Prodrugs, Elsevier (1985)).Hydroxy groups have been masked as esters and ethers. EP 039,051 (Sloanand Little, Apr. 11, 1981) discloses Mannich-base hydroxamic acidprodrugs, their preparation and use.

The specification and claims contain listing of species using thelanguage “selected from . . . and . . . ” and “is . . . or . . . ”(sometimes referred to as Markush groups). When this language is used inthis application, unless otherwise stated it is meant to include thegroup as a whole, or any single members thereof, or any subgroupsthereof. The use of this language is merely for shorthand purposes andis not meant in any way to limit the removal of individual elements orsubgroups as needed.

EXPERIMENTAL

General

Unless otherwise noted, all materials were obtained from commercialsuppliers and used without further purification. All parts are by weightand temperatures are in degrees centigrade unless otherwise indicated.All compounds showed NMR spectra consistent with their assignedstructures. Melting points were determined on a Buchi apparatus and areuncorrected. Mass spectral data was determined by electrosprayionization technique. All examples were purified to ≧95% purity asdetermined by high-performance liquid chromatography. Unless otherwisestated, reactions were run at room temperature under a nitrogenatmosphere. Microwave reactions were conducted using a SmithSynthesizer® (Personal Chemistry, Inc., Upssala, Sweden) apparatus. Thefollowing abbreviations are used: aq. aqueous BINAP2,2′-bis(diphenylphosphino)-1,1′-binaphthyl cond concentrated DMFN,N-dimethylformamide DMSO methyl sulfoxide Et₂O diethyl ether EtOAcethyl acetate EtOH ethyl alcohol h hour min minutes MeOH methyl alcoholsatd saturated THF tetrahydrofuranGeneric Schemes for the Preparation of Pyridazine Core (I):

Generic Schemes for the Preparation of 1,2,4-Triazine Core (II):

Generic Scheme for the Preparation of Pyrazine Core (III):

Generic Scheme for the Preparation of Pyridine Core (IV):

Generic Schemes for the Preparation of Pyridine Core (V):

Example 1

(a) 4-(5-Bromo-pyridin-3-yloxy)-benzothiazol-2-ylamine. A mixture of3,5-dibromopyridine (237 mg, 1 mmol, Aldrich),2-amino-4-hydroxybenzothiazole (183 mg, 1.1 mmol, Astatech, Inc.),Cs₂CO₃ (652 mg, 2.0 mmol), CuI (57 mg, 0.3 mmol), toluene (4 mL) and NMP(1 mL) was heated at 200° C. for 50 min in a microwave. The solvent wasremoved under a N₂ stream and resulting solid was purified by prep LC(10-90% CH₃CN/H₂O modified with 0.1% TFA) to give4-(5-bromo-pyridin-3-yloxy)-benzothiazol-2-ylamine as a brown solid [MS(ESI, pos. ion) m/z: 322 (M+1)].

(b)4-[5-(4-Trifluoromethyl-phenyl)-pyridin-3-yloxy]-benzothiazol-2-ylamine.A mixture of 4-(5-bromo-pyridin-3-yloxy)-benzothiazol-2-ylamine (50 mg,0.16 mmol), 4-(trifluoromethyl)phenylboronic acid (36 mg, 0.19 mmol,Aldrich), Pd(PPh₃)₄ (37 mg, 0.03 mmol), Na₂CO₃ (2M aq., 0.3 mL) anddioxane (2 mL) was heated at 80° C. for 18 h. The resulting mixture wasevaporated under N₂ stream and purified by prep LC (10-90% CH₃CN/H₂Omodified with 0.1% TFA) to give4-[5-(4-trifluoromethyl-phenyl)-pyridin-3-yloxy]-benzothiazol-2-ylamineas a white solid [MS (ESI, pos. ion) m/z: 388 (M+1)].

Example 2

N-{4-[5-(4-Trifluoromethyl-phenyl)-pyridin-3-yloxy]-benzothiazol-2-yl}-acetamide.A solution of4-[5-(4-trifluoromethyl-phenyl)-pyridin-3-yloxy]-benzothiazol-2-ylamine(12 mg, 0.031 mmol), acetic anhydride (10 uL, 0.074 mmol) and pyridine(1 mL) was heated at 60° C. for 18 h. The solution was concentratedunder an N₂ stream and the resulting mixture was purified by prep LC(10-90% CH₃CN/H₂O modified with 0.1% TFA) to giveN-{4-[5-(4-trifluoromethyl-phenyl)-pyridin-3-yloxy]-benzothiazol-2-yl}-acetamideas a white solid [MS (ESI, pos. ion) m/z: 430 (M+1)].

Example 3

(a) 4-(6-Chloro-pyrazin-2-yloxy)-benzothiazol-2-ylamine. A mixture of2,6-dichloropyridine (150 mg, 1.0 mmol, Aldrich),2-amino-4-hydroxybenzothiazole (183 mg, 1.1 mmol, Astatech, Inc.), K₂CO₃(276 mg, 2 mmol), and acetonitrile (4 mL) was heated at 180° C. for 30min in a microwave. The solvent was removed under a N₂ stream and theresulting solid was purified by prep LC (10-90% CH₃CN/H₂O modified with0.1% TFA) to give 4-(6-chloro-pyrazin-2-yloxy)-benzothiazol-2-ylamine asa white solid [MS (ESI, pos. ion) m/z: 279 (M+1)].

(b)4-[6-(4-Trifluoromethyl-phenyl)-pyrazin-2-yloxy]-benzothiazol-2-ylamine.A mixture of 4-(6-chloro-pyrazin-2-yloxy)-benzothiazol-2-ylamine (74 mg,0.27 mmol), 4-(trifluoromethyl)phenylboronic acid (63 mg, 0.32 mmol,Aldrich), Pd(PPh₃)₄ (35 mg, 0.03 mmol), Na₂CO₃ (2M aq., 0.5 mL) anddioxane (3 mL) was heated at 100° C. for 18 h. The resulting mixture wasevaporated under a N₂ stream and purified by prep LC (10-90% CH₃CN/H₂Omodified with 0.1% TFA) to give4-[6-(4-trifluoromethyl-phenyl)-pyrazin-2-yloxy]-benzothiazol-2-ylamineas a white solid [MS (ESI, pos. ion) m/z: 389 (M+1)].

Example 4

N-{4-[6-(4-Trifluoromethyl-phenyl)-pyrazin-2-yloxy]-benzothiazol-2-yl}-acetamide.A solution of4-[6-(4-trifluoromethyl-phenyl)-pyrazin-2-yloxy]-benzothiazol-2-ylamine(42 mg, 0.11 mmol), acetic anhydride (50 uL, 0.53 mmol) and pyridine (2mL) was heated at 70° C. for 18 h. The solution was concentrated under aN₂ stream and the resulting solid was purified by prep LC (10-90%CH₃CN/H₂O modified with 0.1% TFA) to giveN-{4-[6-(4-trifluoromethyl-phenyl)-pyrazin-2-yloxy]-benzothiazol-2-yl}-acetamideas a white solid [MS (ESI, pos. ion) m/z: 431 (M+1)].

Example 5

(a) 2-(4-Trifluoromethylphenyl)-pyridin-4-ylamine. In a 100-mLround-bottomed flask were added 4-amino-2-chloropyridine (AldrichChemical Company) (2.6 g, 20 mmol), tetrakis (triphenylphosphine)palladium (0) (Aldrich Chemical Company) (1.2 g, 1 mmol) and1,2-dimethoxyethane (45 mL). After stirring under nitrogen for 10 min,aqueous Na₂CO₃ (2.3 g in 20 mL of water) and4-trifluoromethylbenzeneboronic acid (4.2 g, 22 mmol) were addedsequentially to the mixture. The reaction was stirred in a 90° C. oilbath for 48 h. 1,2-Dimethoxyethane was evaporated in vacuo and theresidue was partitioned between EtOAc and brine. The aqueous layer wasseparated and extracted with EtOAc (2×50 mL) and the combined EtOAclayer dried over Na₂SO₄ and concentrated in vacuo. Purification by flashchromatography using 2:1 of EtOAc/hexanes as eluent provided the titlecompound as an orange oil. MS (ESI, pos. ion) m/z: 239 (M+1).

(b)(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-[2-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-amine.To an oven-dried 100-mL, round-bottomed flask were added2-(4-trifluoromethylphenyl)-pyridin-4-ylamine (0.18 g, 0.77 mmol) and6-bromo-1,4-benzodioxane (Aldrich Chemical Company) (0.17 g, 0.77 mmol),followed by anhydrous toluene (50 mL). Nitrogen was bubbled through theabove solution via needle for 1 h. Palladium acetate (Aldrich ChemicalCompany) (26 mg, 0.12 mmol) and BINAP (Aldrich Chemical Company) (72 mg,0.12 mmol) were then added to the reaction in one portion, followed bysodium tert-butoxide (Aldrich Chemical Company) (0.21 g, 2.2 mmol). Thereaction mixture was heated in a 90° C. oil bath for 16 h. After coolingto room temperature, the reaction mixture was taken up into ether, andwashed with brine. The aqueous layer was extracted with ether (2×20 mL)and the combined ether layers were dried over Na₂SO₄ and concentrated.The residue was purified on a Biotage 40 S column (2:1 hexane:EtOAc),followed by recrystallization in EtOAc and hexane to provide the titlecompound as a light-yellow solid. MS (ESI, pos. ion) m/z: 373 (M+1).

Example 6

(a) (5-Bromo-pyridin-3-yl)-quinolin-7-yl-amine. A mixture of3,5-dibromo-pyridine (120 mg, 0.5 mmol, Aldrich), Pd(OAc)₂ (11 mg, 0.025mmol, Strem), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (62mg, 0.05 mmol, Strem), K₂CO₃ (690 mg, 5 mmol), 7-aminoquinoline (80 mg,0.55 mmol, Synchem), and toluene (3 mL) was heated at 200° C. for 50 minin a microwave. The solvent was removed under a N₂ stream and resultingsolid was purified by prep LC (10-90% CH₃CN/H₂O modified with 0.1% TFA)to give (5-Bromo-pyridin-3-yl)-quinolin-7-yl-amine as an orange solid[MS (ESI, pos. ion) m/z: 300 (M+1)].

(b) Quinolin-7-yl-[5-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-amine. Amixture of (5-bromo-pyridin-3-yl)-quinolin-7-yl-amine (60 mg, 0.20mmol), 4-(trifluoromethyl)phenylboronic acid (50 mg, 0.26 mmol,Aldrich), Pd(PPh₃)₄ (50 mg, 0.043 mmol), Na₂CO₃ (2M aq., 0.15 mL) anddioxane (2 mL) was heated at 140° C. for 10 min in a microwave. Theresulting mixture was evaporated under N₂ stream and purified by prep LC(10-90% CH₃CN/H₂O modified with 0.1% TFA) to givequinolin-7-yl-[5-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-amine as ayellow solid [MS (ESI, pos. ion) m/z: 366 (M+1)].

Example 7

(a) 4-Chloro-2-(4-trifluoromethyl-phenyl)-pyridine. To a stirredsuspension of anhydrous CuCl₂ (Aldrich, 0.41 g, 3 mmol) in dryacetonitrile (3 mL) in an oven-dried, round-bottomed flask was addedtert-butyl nitrile (Aldrich, 0.45 mL, 3.8 mmol). After stirring at roomtemperature for 10 min, 2-(4-trifluoromethyl-phenyl)-pyridin-4-ylamine(Example 5 (a), 0.6 g, 2.5 mmol) in 2 mL of acetonitrile was addeddropwise. The reaction mixture was stirred at room temperature for 30min, then at 65° C. for 2 h. The mixture was concentrated in vacuo andthe residue was diluted with 10 mL of methylene chloride. Theprecipitate was filtered off, and the filtrate was purified on an ISCO40 g column (1:9 EtOAc/hexanes) to give the title compound as alight-yellow solid. MS (ESI, pos. ion) m/z: 257.9 (M+1).

(b)N-{4-[2-(4-Trifluoromethyl-phenyl)-pyridin-4-yloxy]-benzothiazol-2-yl}-acetamide.To the mixture of 4-chloro-2-(4-trifluoromethyl-phenyl)-pyridine(Example 2 (a), 55 mg, 0.2 mmol) andN-(4-hydroxy-benzothiazol-2-yl)-acetamide (89 mg, 0.4 mmol) inN-methylpyrrolidone (1 mL) in a vial was added potassium t-butoxide (50mg, 0.45 mmol). The vial was put into Emrys microwave and was heated at220° C. for 25 min. The reaction mixture was partitioned between EtOAcand brine. The aqueous layer was separated and back extracted with EtOAc(2×20 mL). The combined EtOAc layer was dried over Na₂SO₄ andconcentrated in vacuo. Purification by flash chromatography using 1:4 ofEtOAc/hexanes as eluent provided the title compound as a white solid. MS(ESI, pos. ion) m/z: 430 (M+1).

Example 8

7-[2-(4-Trifluoromethyl-phenyl)-pyridin-4-yloxy]-quinoline. Thismaterial was prepared following the methods described in Example 8 (b)using 4-chloro-2-(4-trifluoromethyl-phenyl)-pyridine (Example 8 (a), 43mg, 0.16 mmol), 7-hydroxyquinoline (46 mg, 0.32 mmol) and potassiumt-butoxide (38 mg, 0.34 mmol) in N-methylpyrrolidone (0.6 mL). Thecompound was purified by flash chromatography using 1:4 ofEtOAc/hexanes, to provide the title compound as a white solid. MS (ESI,pos. ion) m/z: 367 (M+1).

Example 9

(a) 5-Bromo-N-(2,3-dihydrobenzo[b] [1,4]dioxin-6-yl)pyridin-3-amine. Amixture of 3-bromo-5-iodopyridine (340 mg, 1.19 mmol, Aldrich),6-aminobenzodioxane (300 mg, 1.99 mmol, Aldrich), Pd₂ dba₃ (20 mg, 0.022mmol), 1,1′-bis(diphenyl-phosphino)Ferrocene (DPPF) (20 mg, 0.036 mmol),sodium t-butoxide (140 mg, 1.44 mmol) and toluene (4 mL) was heated at150° C. for 10 min in a microwave. The solvent was removed under reducedpressure and the resulting mixture was purified by silica gelchromatography (1-3% MeOH/DCM) to give5-bromo-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)pyridin-3-amine as alight yellow solid [MS (ESI, pos. ion) m/z: 307, 309 (M+1)].

(b) 5-(4-tert-Butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)pyridin-3-amine. A mixture of5-bromo-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)pyridin-3-amine (154 mg,0.502 mmol), 4-tert-butylphenylboronic acid (107 mg, 0.601 mmol,Aldrich), polystyrene triphenylphosphine palladium (0) (45 mg, 0.11mmol/g, 0.0050 mmol), Na₂CO₃ (2M aq., 0.75 mL) and DME/EtOH (4 mL, 50%)was heated at 120° C. for 5 min in a microwave. The slurry was filtered,the solvent was removed under reduced pressure and the resulting mixturewas purified by silica gel chromatography (10-40% EtOAc/hexane) to give5-(4-tert-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)pyridin-3-amineas an off white solid [MS (ESI, pos. ion) m/z: 361 (M+1)].

Example 10

(a) 6-Bromo-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)pyrazin-2-amine. Thismaterial was made by the method described in Example 9(a). [MS (ESI,pos. ion) m/z: 264 (M+1)]

(b) 6-(4-tert-Butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)pyrazin-2-amine. This material was made by the methoddescribed in Example 9(b). [MS (ESI, pos. ion) m/z: 362 (M+1)].

Example 11

(a) 5-Methoxy-3-(4-(trifluoromethyl)phenyl)pyridazine. A mixture of3-chloro-5-methoxypyridazine (0.146 mg, 1 mmol, (synthesized accordingto the method of Bryant, R. D.; Kunng, F-A. and South, M. S. J.Heterocyclic Chem. 1995, 32, 1473.), 4-(trifluoromethyl)phenylboronicacid (285 mg, 1.5 mmol, Aldrich) in ethylene glycol dimethyl ether (2.0mL) was degassed by bubbling nitrogen through the solution for 15 min.1.5 mL of 2N potassium carbonate andtetrakis(triphenylphosphine)palladium(0) (185 mg, 0.16 mmol, Strem) wereadded and the mixture was heated at 90° C. for 18 h. The reactionmixture was cooled to room temperature and filtered through a pad ofCelite . The resulting crude product was purified by preparative HPLC(1-99% CH₃CN/H₂O modified with 0.1% TFA) to give5-methoxy-3-(4-(trifluoromethyl)phenyl)pyridazine as a tan solid [MS(ESI, pos. ion) m/z: 255 (M+1)].

(b) 6-(4-(Trifluoromethyl)phenyl)pyridazin-4-ol.5-Methoxy-3-(4-(trifluoromethyl)phenyl)pyridazine (136 mg, 0.54 mmol)was dissolved in 2 mL MeOH and 2 mL of 47% HI was added. The reactionmixture was heated to 75° C. for 3 days. The reaction mixture was cooledto room temperature. Solid NaHCO₃ was added to neutralize the mixtureand the MeOH was evaporated. Water was removed with a lyophilizer, andprecipitation was induced by adding water, MeOH, and acetonitrile. Theresulting solid was collected by filtration to afford6-(4-(trifluoromethyl)phenyl)pyridazin-4-ol as a white solid [MS (ESI,pos. ion) m/z: 241 (M+1)].

(c) 5-Chloro-3-(4-(trifluoromethyl)phenyl)pyridazine.6-(4-(Trifluoromethyl)-phenyl)pyridazin-4-ol (59 mg, 0.25 mmol) washeated in phosphorus oxychloride (1.0 mL) at 70° C. for 4 h. The excessphosphorus oxychloride was evaporated under reduced pressure. SaturatedNaHCO₃ was added to the residue and the product was extracted intoCH₂Cl₂. The organic phase was dried over Na₂SO₄, filtered, andconcentrated to afford 5-chloro-3-(4-(trifluoromethyl)phenyl)-pyridazineas a yellow solid [MS (ESI, pos. ion) m/z: 259 (M+1)].

(d)N-(4-(6-(4-(Trifluoromethyl)phenyl)pyridazin-4-yloxy)benzo[d]thiazol-2-yl)acetamide.5-Chloro-3-(4-(trifluoromethyl)phenyl)pyridazine (61 mg, 0.24 mmol),palladium acetate (2.4 mg, 0.011 mmol, Aldrich),2-(di-t-butylphosphino)-biphenyl (2.5 mg, 0.0084 mmol, Strem), potassiumphosphate (105 mg, 0.49 mmol, Aldrich), andN-(4-hydroxybenzo[d]thiazol-2-yl)acetamide (61 mg, 0.294 mmol) weremixed into toluene (2 mL) and heated in a microwave at 180° C. for totalof 3.5 h. The mixture was filtered through Celite™ and the filtrate wasconcentrated. The resulting crude product was purified by preparativeHPLC (1-99% CH₃CN/H₂O modified with 0.1% TFA) to giveN-(4-(6-(4-(trifluoromethyl)-phenyl)pyridazin-4-yloxy)benzo[d]thiazol-2-yl)acetamideas a tan solid [MS (ESI, pos. ion) m/z: 431 (M+1)].

Additional Examples

Following the procedures described above, or with slight modificationsthereof, and following procedures familiar to one of ordinary skill inthe art, the following examples were prepared from commerciallyavailable reagents: MS (ESI, pos. ion) Example Structure m/z 12

367 13

503

Other compounds included in this invention that can be made using theabove methods and procedures are set forth below in Tables 1-5. TABLE 1

Ex # R¹ R⁴ J 1001 {4-[1-(2-fluorophenyl)ethyl]piperazin-1-yl}2-(acetylamino)-1,3- NH benzothiazol-4-yl 1002{4-[ethyl(methyl)amino]phenyl} 2-(acetylamino)-1,3- NH benzothiazol-4-yl1003 1-benzofuran-5-yl quinolin-7-yl NH 10042-({[1-(tert-butoxycarbonyl)piperidin-3- 2-(acetylamino)-1,3- NHyl]carbonyl}amino)-4- benzothiazol-4-yl (trifluoromethyl)phenyl 10052-({[1-(tert-butoxycarbonyl)piperidin-4- 2-(acetylamino)-1,3- NHyl]methyl}amino)-4-(trifluoromethyl)phenyl benzothiazol-4-yl 10062-(2-pyrrolidin-1-ylethoxy)-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 10072-(benzylamino)-4-(trifluoromethyl)phenyl quinolin-7-yl NH 10082-(benzyloxy)4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1009 2-(isonicotinoylamino)-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 10102-(lactoylamino)-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- NH4-yl 1011 2-(methoxycarbonyl)-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 1012 2-(methoxymethoxy)-4-2-amino-1,3-benzothiazol- NH (trifluoromethyl)phenyl 4-yl 10132-(methylamino)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1014 2-(pentylamino)-4-(trifluoromethyl)phenylquinolin-7-yl NH 1015 2,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl2-(acetylamino)-1,3- NH benzothiazol-4-yl 10162,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl 2-amino-1,3-benzothiazol- NH4-yl 1017 2-[(2,2-dimethylpropanoyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 10182-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 10192-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-amino-1,3-benzothiazol- NH(trifluoromethyl)phenyl 4-yl 10202-[(3-piperidin-1-ylpropanoyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol4-yl 10212-[(4-tert-butylbenzyl)amino]-4- quinolin-7-yl NH(trifluoromethyl)phenyl 1022 2-[(cyclohexylacetyl)amino]-4-2-(acetylamino)-1,3- NH (trifluoromethyl)phenyl benzothiazol-4-yl 10232-[(cyclohexylcarbonyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 10242-[(cyclohexylmethyl)amino]-4- 1,3-benzothiazol-6-yl NH(trifluoromethyl)phenyl 1025 2-[(cyclohexylmethyl)amino]-4-quinolin-7-yl NH (trifluoromethyl)phenyl 10262-[(cyclohexylmethyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 10272-[(cyclohexylmethyl)amino]-6- quinolin-7-yl NH(trifluoromethyl)pyridin-3-yl 1028 2-[(cyclopentylacetyl)amino]4-2-(acetylamino)-1,3- NH (trifluoromethyl)phenyl benzothiazol-4-yl 10292-[(cyclopropylcarbonyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 10302-[(N,N-dimethylglycyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 10312-[(piperidin-3-ylmethyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 10322-[(pyridin-3-ylcarbonyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 10332-[(pyridin-4-ylmethyl)amino]-4- quinolin-7-yl NH(trifluoromethyl)phenyl 1034 2-[tert-butoxycarbonyl)amino]-4-quinolin-7-yl NH (trifluoromethyl)phenyl 10352-[(tert-butoxycarbonyl)amino]-4- 2-aminoquinolin-8-yl NH(trifluoromethyl)phenyl 1036 2-[(tert-butoxycarbonyl)amino]-4-2-(acetylamino)-1,3- NH (trifluoromethyl)phenyl benzothiazol-4-yl 10372-[2-(dimethylamino)ethoxy]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 10382-{[(1-acetylpiperidin-4-yl)carbonyl]amino}- 2-(acetylamino)-1,3 - NH4-(trifluoromethyl)phenyl benzothiazol-4-yl 10392-{[(1-methyl-1H-imidazol-5- 2-(acetylamino)-1,3- NH yl)carbonyl]amino}-benzothiazol-4-yl (trifluoromethyl)phenyl 1040 2-{[(1-methylpiperidin-4-2-(acetylamino)-1,3- NH yl)carbonyl]amino}-4- benzothiazol-4-yl(trifluoromethyl)phenyl 1041 2-{[(1-propylpiperidin-4-yl)methyl]amino}-2-(acetylamino)-1,3- NH 4-(trifluoromethyl)phenyl benzothiazol-4-yl 10422-{[(4-{[tert- 2-(acetylamino)-1,3- NHbutyl(dimethyl)silyl]oxy}cyclohexyl) benzothiazol-4-ylcarbonyl]amino}-4- (trifluoromethyl)phenyl 10432-{[(4-hydroxycyclohexyl)carbonyl]amino}- 2-(acetylamino)-1,3- NH4-(trifluorometbyl)phenyl benzothiazol-4-yl 10442-{[hydroxy(phenyl)acetyl]amino}-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 10452-{[hydroxy(phenyl)acetyl]amino}-4- 2-amino-1,3-benzothiazol- NH(trifluoromethyl)phenyl 4-yl 1046 2-amino-4-(trifluoromethyl)phenylquinolin-7-yl NH 1047 2-amino-4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl NH 1048 2-amino-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 10492-bromo-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1050 2-chloro-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 10512-hydroxy-4-(trifluoromethyl)phenyl quinolin-7-yl NH 10522-hydroxy-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- NH 4-yl1053 2-hydroxy-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1054 2-iodo-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 1055 2-naphthyl quinolin-7-ylNH 1056 2-piperidin-1-yl-6-(trifluoromethyl)pyridin- quinolin-7-yl NH3-yl 1057 3-(trifluoromethoxy)phenyl quinolin-7-yl NH 10583-(trifluoromethoxy)phenyl 2-aminoquinolin-8-yl NH 10593,4-difluorophenyl quinolin-7-yl NH 1060 3-chloro-4-fluorophenylquinolin-7-yl NH 1061 3-fluoro-4-methylphenyl quinolin-7-yl NH 10624-(1-phenylethyl)piperazin-1-yl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1063 4-(2-fluorophenyl)piperazin-1-yl2-(acetylamino)-1,3- NH benzothiazol-4-yl 1064 4-(dimethylamino)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 10654-(trifluoromethoxy)phenyl quinolin-7-yl NH 10664-(trifluoromethoxy)phenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl1067 4-(trifluoromethyl)-2- 2-(acetylamino)-1,3- NH{[(trifluoromethyl)sulfonyl]oxy}phenyl benzothiazol-4-yl 10684-(trifluoromethyl)-2-{[4- 2-(acetylamino)-1,3- NH(trifluoromethyl)benzoyl]amino }phenyl benzothiazol-4-yl 10694-(trifluoromethyl)cyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- NH 4-yl1070 4-(trifluoromethyl)cyclohex-1-en-1-yl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1071 4-(trifluoromethyl)phenyl 1,3-benzothiazol-4-ylNH 1072 4-(trifluoromethyl)phenyl 1,3-benzothiazol-5-yl NH 10734-(trifluoromethyl)phenyl 1H-benzimidazol-5-yl NH 10744-(trifluoromethyl)phenyl 1H-indazol-5-yl NH 10754-(trifluoromethyl)phenyl 1H-indol-4-yl NH 10764-(trifluoromethyl)phenyl 1H-indol-5-yl NH 10774-(trifluoromethyl)phenyl 1-methyl-2-oxo-1,2- NH dihydroquinoxalin-5-yl1078 4-(trifluoromethyl)phenyl 1-naphthyl NH 10794-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 10804-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NH benzoxazol-4-yl 10814-(trifluoromethyl)phenyl 2-(acetylamino)quinolin-8- NH 10824-(trifluoromethyl)phenyl 2-(aminocarbonyl)-1,3- NH benzothiazol-4-yl1083 4-(trifluoromethyl)phenyl 2-(hydroxymethyl)-2,3- NHdihydro-1,4-benzodioxin-6- 1084 4-(trifluoromethyl)phenyl2-(lactoylamino)-1,3- NH benzothiazol-4-yl 10854-(trifluoromethyl)phenyl 2-(methylamino)quinolin-8- NH yl 10864-(trifluoromethyl)phenyl 2-(pyridin-2-ylamino)-1,3- NHbenzothiazol-4-yl 1087 4-(trifluoromethyl)phenyl 2,3-dihydro-1,4- NHbenzodioxin-6-yl 1088 4-(trifluoromethyl)phenyl2,3-dimethyl-1H-indol-6-yl NH 1089 4-(trifluoromethyl)phenyl2,6-diamino-1,3- NH benzothiazol-4-yl 1090 4-(trifluoromethyl)phenyl2-amino-1,3-benzothiazol- NH 4-yl 1091 4-(trifluoromethyl)phenyl2-aminoimidazo[1,2- NH a]pyridin-8-yl 1092 4-(trifluoromethyl)phenyl2-aminoquinazolin-8-yl NH 1093 4-(trifluoromethyl)phenyl2-aminoquinolin-7-yl NH 1094 4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl NH 1095 4-(trifluoromethyl)phenyl2-aminoquinoxalin-5-yl NH 1096 4-(trifluoromethyl)phenyl2-chloro-1,3-benzothiazol- NH 4-yl 1097 4-(trifluoromethyl)phenyl2-chloroquinolin-8-yl NH 1098 4-(trifluoromethyl)phenyl 2-hydroxy-1,3-NH benzothiazol-4-yl 1099 4-(trifluoromethyl)phenyl 2-hydroxy-4- NHmethylquinolin-7-yl 1100 4-(trifluoromethyl)phenyl2-hydroxyquinolin-7-yl NH 1101 4-(trifluoromethyl)phenyl2-hydroxyquinoxalin-5-yl NH 1102 4-(trifluoromethyl)phenyl2-methyl-1,3-benzothiazol- NH 5-yl 1103 4-(trifluoromethyl)phenyl2-naphthyl NH 1104 4-(trifluoromethyl)phenyl 2-oxo-1,2,3,4- NHtetrahydroquinolin-7-yl 1105 4-(trifluoromethyl)phenyl 2-oxo-1,2,3,4- NHtetrahydroquinoxalin-5-yl 1106 4-(trifluoromethyl)phenyl2-pyridin-4-yl-1,3- NH benzothiazol-4-yl 1107 4-(trifluoromethyl)phenyl3-(1-hydroxy-1- NH methylethyl)quinolin-7-yl 11084-(trifluoromethyl)phenyl 3-(1-hydroxyethyl)quinolin- NH 7-yl 11094-(trifluoromethyl)phenyl 3-(hydroxymethyl)-1,2,3,4- NHtetrahydroquinolin-7-yl 1110 4-(trifluoromethyl)phenyl3-(hydroxymethyl)-2-oxo- NH 1,2,3,4-tetrahydroquinolin- 7-yl 11114-(trifluoromethyl)phenyl 3-(hydroxymethyl)quinolin- NH 7-yl 11124-(trifluoromethyl)phenyl 3- NH (methoxycarbonyl)quinolin 7-yl 11134-(trifluoromethyl)phenyl 3,4-dimethylphenyl NH 11144-(trifluoromethyl)phenyl 3-amino-2-oxo-1,2- NH dihydroquinoxalin-5-yl1115 4-(trifluoromethyl)phenyl 3-aminoquinoxalin-5-yl NH 11164-(trifluoromethyl)phenyl 3-chloro-2-methylphenyl NH 11174-(trifluoromethyl)phenyl 3-oxo-1,2,3,4- NH tetrahydroisoquinolin-8-yl1118 4-(trifluoromethyl)phenyl 4-(methylamino)quinazolin- NH 8-yl 11194-(trifluoromethyl)phenyl 4-aminoquinazolin-8-yl NH 11204-(trifluoromethyl)phenyl 4-methylquinolin-8-yl NH 11214-(trifluoromethyl)phenyl isoquinolin-5-yl NH 11224-(trifluoromethyl)phenyl isoquinolin-8-yl NH 11234-(trifluoromethyl)phenyl quinolin-5-yl NH 11244-(trifluoromethyl)phenyl quinolin-7-yl NH 11254-(trifluoromethyl)phenyl quinolin-8-yl NH 11264-(trifluoromethyl)piperidin-1-yl 2-amino-1,3-benzothiazol- NH 4-yl 11274-acetylphenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 11284-acetylphenyl 2-amino-1,3-benzothiazol- NH 4-yl 11294-benzylpiperazin-1-yl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 11304-bromophenyl quinolin-7-yl NH 1131 4-bromophenyl2-amino-1,3-benzothiazol- NH 4-yl 1132 4-bromophenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 1133 4-chlorophenylquinolin-7-yl NH 1134 4′-fluoro-5-(trifluoromethyl)-1,1′- quinolin-7-ylNH biphenyl-2-yl 1135 4-fluorophenyl quinolin-7-yl NH 11364-methylphenyl 2-amino-1,3-benzothiazol- NH 4-yl 1137 4-methylphenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 1138 4-phenylpiperazin-1-yl2-(acetylamino)-1,3- NH benzothiazol4-yl 11394-tert-butylcyclohex-1-en-1-yl 2-(acetylamino)-1,3- NH benzothiazol-4-yl1140 4-tert-butylcyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- NH 4-yl1141 4-tert-butylphenyl 2,3-dihydro-1,4- NH benzodioxin-6-yl 11424-tert-butylphenyl 1H-1,2,3-benzotriazol-6-yl NH 1143 4-tert-butylphenyl3-methoxyphenyl NH 1144 4-tert-butylphenyl quinolin-7-yl NH 11454-tert-butylphenyl 1,3-benzothiazol-6-yl NH 1146 4-tert-butylphenylquinolin-7-yl NH 1147 4-tert-butylphenyl 2-methyl-1,3-benzothiazol- NH5-yl 1148 4-tert-butylphenyl 2-amino-1,3-benzothiazol- NH 4-yl 11494-tert-butylphenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 1150{4-[1-(2-fluorophenyl)ethyl]piperazin-1-yl} 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1151 {4-[ethyl(methyl)amino]phenyl}2-(acetylamino)-1,3- O benzothiazol-4-yl 1152 1-benzofuran-5-ylquinolin-7-yl O 1153 2-({[1-(tert-butoxycarbonyl)piperidin-3-2-(acetylamino)-1,3- O yl]carbonyl}amino)-4- benzothiazol-4-yl(trifluoromethyl)phenyl 1154 2-({[1-(tert-butoxycarbonyl)piperidin-4-2-(acetylamino)-1,3- O yl]methyl}amino)-4-(trifluoromethyl)phenylbenzothiazol-4-yl 1155 2-(2-pyrrolidin-1-ylethoxy)-4-2-(acetylamino)-1,3- O (trifluoromethyl)phenyl benzothiazol-4-yl 11562-(benzylamino)-4-(trifluoromethyl)phenyl quinolin-7-yl O 11572-(benzyloxy)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1158 2-(isonicotinoylamino)-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11592-(lactoylamino)-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- O4-yl 1160 2-(methoxycarbonyl)-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 1161 2-(methoxymethoxy)-4-2-amino-1,3-benzothiazol- O (trifluoromethyl)phenyl 4-yl 11622-(methylamino)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1163 2-(pentylamino)-4-(trifluoromethyl)phenylquinolin-7-yl O 1164 2,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl2-(acetylamino)-1,3 - O benzothiazol-4-yl 11652,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl 2-amino-1,3-benzothiazol- O4-yl 1166 2-[(2,2-dimethylpropanoyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11672-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11682-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-amino-1,3-benzothiazol- O(trifluoromethyl)phenyl 4-yl 11692-[(3-piperidin-1-ylpropanoyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11702-[(4-tert-butylbenzyl)amino]-4- quinolin-7-yl O (trifluoromethyl)phenyl1171 2-[(cyclohexylacetyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11722-[(cyclohexylcarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11732-[(cyclohexylmethyl)amino]-4- 1,3-benzothiazol-6-yl O(trifluoromethyl)phenyl 1174 2-[(cyclohexylmethyl)amino]-4-quinolin-7-yl O (trifluoromethyl)phenyl 11752-[(cyclohexylmethyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11762-[(cyclohexylmethyl)amino]-6- quinolin-7-yl O(trifluoromethyl)pyridin-3-yl 1177 2-[(cyclopentylacetyl)amino]-4-2-(acetylamino)-1,3- O (trifluoromethyl)phenyl benzothiazol-4-yl 11782-[(cyclopropylcarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11792-[(N,N-dimethylglycyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11802-[(piperidin-3-ylmethyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11812-[(pyridin-3-ylcarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11822-[(pyridin-4-ylmethyl)amino]-4- quinolin-7-yl O (trifluoromethyl)phenyl1183 2-[(tert-butoxycarbonyl)amino]-4- quinolin-7-yl O(trifluoromethyl)phenyl 1184 2-[(tert-butoxycarbonyl)amino]-4-2-aminoquinolin-8-yl O (trifluoromethyl)phenyl 11852-[(tert-butoxycarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11862-[2-(dimethylamino)ethoxy]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11872-{[(1-acetylpiperidin-4-yl)carbonyl]amino }- 2-(acetylamino)-1,3- O4-(trifluoromethyl)phenyl benzothiazol-4-yl 11882-{[(1-methyl-1H-imidazol-5- 2-(acetylamino)-1,3- Oyl)carbonyl]amino}-4- benzothiazol-4-yl (trifluoromethyl)phenyl 11892-{[(1-methylpiperidin-4- 2-(acetylamino)-1,3- O yl)carbonyl]amino }-4-benzothiazol-4-yl (trifluoromethyl)phenyl 11902-{[(1-propylpiperidin-4-yl)methyl]amino}- 2-(acetylamino)-1,3- O4-(trifluoromethyl)phenyl benzothiazol-4-yl 1191 2-{[(4-{[tert-2-(acetylamino)-1,3- O butyl(dimethyl)silyl]oxy}cyclohexyl)benzothiazol-4-yl carbonyl]amino }-4- (trifluoromethyl)phenyl 11922-{[(4-hydroxycyclohexyl)carbonyl]amino}- 2-(acetylamino)-1,3- O4-(trifluoromethyl)phenyl benzothiazol-4-yl 11932-{[hydroxy(phenyl)acetyl]amino}-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 11942-{[hydroxy(phenyl)acetyl]amino}-4- 2-amino-1,3-benzothiazol- O(trifluoromethyl)phenyl 4-yl 1195 2-amino-4-(trifluoromethyl)phenylquinolin-7-yl O 1196 2-amino-4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl O 1197 2-amino-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 11982-bromo-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1199 2-chloro-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 12002-hydroxy-4-(trifluoromethyl)phenyl quinolin-7-yl O 12012-hydroxy-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- O 4-yl1202 2-hydroxy-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1203 2-iodo-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 1204 2-naphthyl quinolin-7-yl O1205 2-piperidin-1-yl-6-(trifluoromethyl)pyridin- quinolin-7-yl O 3-yl1206 3-(trifluoromethoxy)phenyl quinolin-7-yl O 12073-(trifluoromethoxy)phenyl 2-aminoquinolin-8-yl O 12083,4-difluorophenyl quinolin-7-yl O 1209 3-chloro-4-fluorophenylquinolin-7-yl O 1210 3-fluoro-4-methylphenyl quinolin-7-yl O 12114-(1-phenylethyl)piperazin-1-yl 2-(acetylamino)-1,3- O benzothiazol-4-yl1212 4-(2-fluorophenyl)piperazin-1-yl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1213 4-(dimethylamino)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1214 4-(trifluoromethoxy)phenyl quinolin-7-yl O 12154-(trifluoromethoxy)phenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 12164-(trifluoromethyl)-2- 2-(acetylamino)-1,3- O{[(trifluoromethyl)sulfonyl]oxy}phenyl benzothiazol-4-yl 12174-(trifluoromethyl)-2-{[4- 2-(acetylamino)-1,3- O(trifluoromethyl)benzoyl]amino}phenyl benzothiazol-4-yl 12184-(trifluoromethyl)cyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- O 4-yl1219 4-(trifluoromethyl)cyclohex-1-en-1-yl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1220 4-(trifluoromethyl)phenyl 1,3-benzothiazol-4-yl O1221 4-(trifluoromethyl)phenyl 1,3-benzothiazol-5-yl O 12224-(trifluoromethyl)phenyl 1H-benzimidazol-5-yl O 12234-(trifluoromethyl)phenyl 1H-indazol-5-yl O 12244-(trifluoromethyl)phenyl 1H-indol-4-yl O 1225 4-(trifluoromethyl)phenyl1H-indol-5-yl O 1226 4-(trifluoromethyl)phenyl 1-methyl-2-oxo-1,2- Odihydroquinoxalin-5-yl 1227 4-(trifluoromethyl)phenyl 1-naphthyl O 12284-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 12294-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- O benzoxazol-4-yl 12304-(trifluoromethyl)phenyl 2-(acetylamino)quinolin-8- O yl 12314-(trifluoromethyl)phenyl 2-(aminocarbonyl)-1,3- O benzothiazol-4-yl1232 4-(trifluoromethyl)phenyl 2-(hydroxymethyl)-2,3- Odihydro-1,4-benzodioxin-6- yl 1233 4-(trifluoromethyl)phenyl2-(lactoylamino)-1,3- O benzothiazol-4-yl 1234 4-(trifluoromethyl)phenyl2-(methylamino)quinolin-8- O yl 1235 4-(trifluoromethyl)phenyl2-(pyridin-2-ylamino)-1,3- O benzothiazol-4-yl 12364-(trifluoromethyl)phenyl 2,3-dihydro-1,4- O benzodioxin-6-yl 12374-(trifluoromethyl)phenyl 2,3-dimethyl-1H-indol-6-yl O 12384-(trifluoromethyl)phenyl 2,6-diamino-1,3- O benzothiazol-4-yl 12394-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- O 4-yl 12404-(trifluoromethyl)phenyl 2-aminoimidazo[1,2- O a]pyridin-8-yl 12414-(trifluoromethyl)phenyl 2-aminoquinazolin-8-yl O 12424-(trifluoromethyl)phenyl 2-aminoquinolin-7-yl O 12434-(trifluoromethyl)phenyl 2-aminoquinolin-8-yl O 12444-(trifluoromethyl)phenyl 2-aminoquinoxalin-5-yl O 12454-(trifluoromethyl)phenyl 2-chloro-1,3-benzothiazol- O 4-yl 12464-(trifluoromethyl)phenyl 2-chloroquinolin-8-yl O 12474-(trifluoromethyl)phenyl 2-hydroxy-1,3- O benzothiazol-4-yl 12484-(trifluoromethyl)phenyl 2-hydroxy-4- O methylquinolin-7-yl 12494-(trifluoromethyl)phenyl 2-hydroxyquinolin-7-yl O 12504-(trifluoromethyl)phenyl 2-hydroxyquinoxalin-5-yl O 12514-(trifluoromethyl)phenyl 2-methyl-1,3-benzothiazol- O 5-yl 12524-(trifluoromethyl)phenyl 2-naphthyl O 1253 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- O tetrahydroquinolin-7-yl 1254 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- O tetrahydroquinoxalin-5-yl 12554-(trifluoromethyl)phenyl 2-pyridin-4-yl-1,3- O benzothiazol-4-yl 12564-(trifluoromethyl)phenyl 3-(1-hydroxy-1- O methylethyl)quinolin-7-yl1257 4-(trifluoromethyl)phenyl 3-(1-hydroxyethyl)quinolin- O 7-yl 12584-(trifluoromethyl)phenyl 3-(hydroxymethyl)-1,2,3,4- Otetrahydroquinolin-7-yl 1259 4-(trifluoromethyl)phenyl3-(hydroxymethyl)-2-oxo- O 1,2,3,4-tetrahydroquinolin- 7-yl 12604-(trifluoromethyl)phenyl 3-(hydroxymethyl)quinolin- O 7-yl 12614-(trifluoromethyl)phenyl 3- O (methoxycarbonyl)quinolin- 7-yl 12624-(trifluoromethyl)phenyl 3,4-dimethylphenyl O 12634-(trifluoromethyl)phenyl 3-amino-2-oxo-1,2- O dihydroquinoxalin-5-yl1264 4-(trifluoromethyl)phenyl 3-aminoquinoxalin-5-yl O 12654-(trifluoromethyl)phenyl 3-chloro-2-methylphenyl O 12664-(trifluoromethyl)phenyl 3-oxo-1,2,3,4- O tetrahydroisoquinolin-8-yl1267 4-(trifluoromethyl)phenyl 4-(methylamino)quinazolin- O 8-yl 12684-(trifluoromethyl)phenyl 4-aminoquinazolin-8-yl O 12694-(trifluoromethyl)phenyl 4-methylquinolin-8-yl O 12704-(trifluoromethyl)phenyl isoquinolin-5-yl O 12714-(trifluoromethyl)phenyl isoquinolin-8-yl O 12724-(trifluoromethyl)phenyl quinolin-5-yl O 1273 4-(trifluoromethyl)phenylquinolin-7-yl O 1274 4-(trifluoromethyl)phenyl quinolin-8-yl O 12754-(trifluoromethyl)piperidin-1-yl 2-amino-1,3-benzothiazol- O 4-yl 12764-acetylphenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 12774-acetylphenyl 2-amino-1,3-benzothiazol- O 4-yl 12784-benzylpiperazin-1-yl 2-(acetylamino)-1,3- O benzothiazol-4-yl 12794-bromophenyl quinolin-7-yl O 1280 4-bromophenyl2-amino-1,3-benzothiazol- O 4-yl 1281 4-bromophenyl 2-(acetylamino)-1,3-O benzothiazol-4-yl 1282 4-chlorophenyl quinolin-7-yl O 12834′-fluoro-5-(trifluoromethyl)-1,1′- quinolin-7-yl O biphenyl-2-yl 12844-fluorophenyl quinolin-7-yl O 1285 4-methylphenyl2-amino-1,3-benzothiazol- O 4-yl 1286 4-methylphenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 1287 4-phenylpiperazin-1-yl2-(acetylamino)-1,3- O benzothiazol-4-yl 12884-tert-butylcyclohex-1-en-1-yl 2-(acetylamino)-1,3- O benzothiazol-4-yl1289 4-tert-butylcyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- O 4-yl1290 4-tert-butylphenyl 2,3-dihydro-1,4- O benzodioxin-6-yl 12914-tert-butylphenyl 1H-1,2,3-benzotriazol-6-yl O 1292 4-tert-butylphenyl3-methoxyphenyl O 1293 4-tert-butylphenyl quinolin-7-yl O 12944-tert-butylphenyl 1,3-benzothiazol-6-yl O 1295 4-tert-butylphenylquinolin-7-yl O 1296 4-tert-butylphenyl 2-methyl-1,3-benzothiazol- O5-yl 1297 4-tert-butylphenyl 2-amino-1,3-benzothiazol- O 4-yl 12984-tert-butylphenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 1299{4-[1-(2-fluorophenyl)ethyl]piperazin-1-yl} 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1300 {4-[ethyl(methyl)amino]phenyl}2-(acetylamino)-1,3- S benzothiazol-4-yl 1301 1-benzofuran-5-ylquinolin-7-yl S 1302 2-({[1-(tert-butoxycarbonyl)piperidin-3-2-(acetylamino)-1,3- S yl]carbonyl}amino)-4- benzothiazol-4-yl(trifluoromethyl)phenyl 1303 2-({[1-(tert-butoxycarbonyl)piperidin-4-2-(acetylamino)-1,3- S yl]methyl}amino)-4-(trifluoromethyl)phenylbenzothiazol-4-yl 1304 2-(2-pyrrolidin-1-ylethoxy)-4-2-(acetylamino)-1,3- S (trifluoromethyl)phenyl benzothiazol-4-yl 13052-(benzylamino)-4-(trifluoromethyl)phenyl quinolin-7-yl S 13062-(benzyloxy)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1307 2-(isonicotinoylamino)-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13082-(lactoylamino)-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- S4-yl 1309 2-(methoxycarbonyl)-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 1310 2-(methoxymethoxy)-4-2-amino-1,3-benzothiazol- S (trifluoromethyl)phenyl 4-yl 13112-(methylamino)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1312 2-(pentylamino)-4-(trifluoromethyl)phenylquinolin-7-yl S 1313 2,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl2-(acetylamino)-1,3- S benzothiazol-4-yl 13142,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl 2-amino-1,3-benzothiazol- S4-yl 1315 2-[(2,2-dimethylpropanoyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13162-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13172-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-amino-1,3-benzothiazol- S(trifluoromethyl)phenyl 4-yl 13182-[(3-piperidin-1-ylpropanoyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13192-[(4-tert-butylbenzyl)amino]-4- quinolin-7-yl S (trifluoromethyl)phenyl1320 2-[(cyclohexylacetyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13212-[(cyclohexylcarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13222-[(cyclohexylmethyl)amino]-4- 1,3-benzothiazol-6-yl S(trifluoromethyl)phenyl 1323 2-[(cyclohexylmethyl)amino]-4-quinolin-7-yl S (trifluoromethyl)phenyl 13242-[(cyclohexylmethyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13252-[(cyclohexylmethyl)amino]-6- quinolin-7-yl S(trifluoromethyl)pyridin-3-yl 1326 2-[(cyclopentylacetyl)amino]-4-2-(acetylamino)-1,3- S (trifluoromethyl)phenyl benzothiazol-4-yl 13272-[(cyclopropylcarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13282-[(N,N-dimethylglycyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13292-[(piperidin-3-ylmethyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13302-[(pyridin-3-ylcarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13312-[(pyridin-4-ylmethyl)amino]-4- quinolin-7-yl S (trifluoromethyl)phenyl1332 2-[(tert-butoxycarbonyl)amino]-4- quinolin-7-yl S(trifluoromethyl)phenyl 1333 2-[(tert-butoxycarbonyl)amino]-4-2-aminoquinolin-8-yl S (trifluoromethyl)phenyl 13342-[(tert-butoxycarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13352-[2-(dimethylamino)ethoxy]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13362-{[(1-acetylpiperidin-4-yl)carbonyl]amino}- 2-(acetylamino)-1,3- S4-(trifluoromethyl)phenyl benzothiazol-4-yl 13372-{[(1-methyl-1H-imidazol-5- 2-(acetylamino)-1,3- Syl)carbonyl]amino}-4- benzothiazol-4-yl (trifluoromethyl)phenyl 13382-{[(1-methylpiperidin-4- 2-(acetylamino)-1,3- S yl)carbonyl]amino}-benzothiazol-4-yl (trifluoromethyl)phenyl 13392-{[(1-propylpiperidin-4-yl)methyl]amino }- 2-(acetylamino)-1,3- S4-(trifluoromethyl)phenyl benzothiazol-4-yl 1340 2-{[(4-{[tert-2-(acetylamino)-1,3- S butyl(dimethyl)silyl]oxy}cyclohexyl)benzothiazol-4-yl carbonyl]amino }-4- (trifluoromethyl)phenyl 13412-{[(4-hydroxycyclohexyl)carbonyl]amino}- 2-(acetylamino)-1,3- S4-(trifluoromethyl)phenyl benzothiazol-4-yl 13422-{[hydroxy(phenyl)acetyl]amino}-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 13432-{[hydroxy(phenyl)acetyl]amino }-4- 2-amino-1,3-benzothiazol- S(trifluoromethyl)phenyl 4-yl 1344 2-amino-4-(trifluoromethyl)phenylquinolin-7-yl S 1345 2-amino-4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl S 1346 2-amino-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 13472-bromo-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1348 2-chloro-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 13492-hydroxy-4-(trifluoromethyl)phenyl quinolin-7-yl S 13502-hydroxy-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- S 4-yl1351 2-hydroxy-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1352 2-iodo-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 1353 2-naphthyl quinolin-7-yl S1354 2-piperidin-1-yl-6-(trifluoromethyl)pyridin- quinolin-7-yl S 3-yl1355 3-(trifluoromethoxy)phenyl quinolin-7-yl S 13563-(trifluoromethoxy)phenyl 2-aminoquinolin-8-yl S 13573,4-difluorophenyl quinolin-7-yl S 1358 3-chloro-4-fluorophenylquinolin-7-yl S 1359 3-fluoro-4-methylphenyl quinolin-7-yl S 13604-(1-phenylethyl)piperazin-1-yl 2-(acetylamino)-1,3- S benzothiazol-4-yl1361 4-(2-fluorophenyl)piperazin-1-yl 2-(acetylamino)-1,3- 5benzothiazol-4-yl 1362 4-(dimethylamino)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1363 4-(trifluoromethoxy)phenyl quinolin-7-yl S 13644-(trifluoromethoxy)phenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl 13654-(trifluoromethyl)-2- 2-(acetylamino)-1,3- S{[(trifluoromethyl)sulfonyl]oxy}phenyl benzothiazol-4-yl 13664-(trifluoromethyl)-2-{[4- 2-(acetylamino)-1,3- S(trifluoromethyl)benzoyl]amino}phenyl benzothiazol-4-yl 13674-(trifluoromethyl)cyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- S 4-yl1368 4-(trifluoromethyl)cyclohex-1-en-1-yl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1369 4-(trifluoromethyl)phenyl 1,3-benzothiazol-4-yl S1370 4-(trifluoromethyl)phenyl 1,3-benzothiazol-5-yl S 13714-(trifluoromethyl)phenyl 1H-benzimidazol-5-yl S 13724-(trifluoromethyl)phenyl 1H-indazol-5-yl S 13734-(trifluoromethyl)phenyl 1H-indol-4-yl S 1374 4-(trifluoromethyl)phenyl1H-indol-5-yl S 1375 4-(trifluoromethyl)phenyl 1-methyl-2-oxo-1,2- Sdihydroquinoxalin-5-yl 1376 4-(trifluoromethyl)phenyl 1-naphthyl S 13774-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl 13784-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- S benzoxazol-4-yl 13794-(trifluoromethyl)phenyl 2-(acetylamino)quinolin-8- S yl 13804-(trifluoromethyl)phenyl 2-(aminocarbonyl)-1,3- S benzothiazol-4-yl1381 4-(trifluoromethyl)phenyl 2-(hydroxymethyl)-2,3- Sdihydro-1,4-benzodioxin-6-yl 1382 4-(trifluoromethyl)phenyl2-(lactoylamino)-1,3- S benzothiazol-4-yl 1383 4-(trifluoromethyl)phenyl2-(methylamino)quinolin-8-yl S 1384 4-(trifluoromethyl)phenyl2-(pyridin-2-ylamino)-1,3- S benzothiazol-4-yl 13854-(trifluoromethyl)phenyl 2,3-dihydro-1,4- S benzodioxin-6-yl 13864-(trifluoromethyl)phenyl 2,3-dimethyl-1H-indol-6-yl S 13874-(trifluoromethyl)phenyl 2,6-diamino-1,3- S benzothiazol-4-yl 13884-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- S 4-yl 13894-(trifluoromethyl)phenyl 2-aminoimidazo[1,2- S a]pyridin-8-yl 13904-(trifluoromethyl)phenyl 2-aminoquinazolin-8-yl S 13914-(trifluoromethyl)phenyl 2-aminoquinolin-7-yl S 13924-(trifluoromethyl)phenyl 2-aminoquinolin-8-yl S 13934-(trifluoromethyl)phenyl 2-aminoquinoxalin-5-yl S 13944-(trifluoromethyl)phenyl 2-chloro-1,3-benzothiazol- S 4-yl 13954-(trifluoromethyl)phenyl 2-chloroquinolin-8-yl S 13964-(trifluoromethyl)phenyl 2-hydroxy-1,3- S benzothiazol-4-yl 13974-(trifluoromethyl)phenyl 2-hydroxy-4- S methylquinolin-7-yl 13984-(trifluoromethyl)phenyl 2-hydroxyquinolin-7-yl S 13994-(trifluoromethyl)phenyl 2-hydroxyquinoxalin-5-yl S 14004-(trifluoromethyl)phenyl 2-methyl-1,3-benzothiazol- S 5-yl 14014-(trifluoromethyl)phenyl 2-naphthyl S 1402 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- S tetrahydroquinolin-7-yl 1403 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- S tetrahydroquinoxalin-5-yl 14044-(trifluoromethyl)phenyl 2-pyridin-4-yl-1,3- S benzothiazol-4-yl 14054-(trifluoromethyl)phenyl 3-(1-hydroxy-1- S methylethyl)quinolin-7-yl1406 4-(trifluoromethyl)phenyl 3-(1-hydroxyethyl)quinolin- S 7-yl 14074-(trifluoromethyl)phenyl 3-(hydroxymethyl)-1,2,3,4- Stetrahydroquinolin-7-yl 1408 4-(trifluoromethyl)phenyl3-(hydroxymethyl)-2-oxo- S 1,2,3,4-tetrahydroquinolin- 7-yl 14094-(trifluoromethyl)phenyl 3-(hydroxymethyl)quinolin- S 7-yl 14104-(trifluoromethyl)phenyl 3- S (methoxycarbonyl)quinolin- 7-yl 14114-(trifluoromethyl)phenyl 3,4-dimethylphenyl S 14124-(trifluoromethyl)phenyl 3-amino-2-oxo-1,2- S dihydroquinoxalin-5-yl1413 4-(trifluoromethyl)phenyl 3-aminoquinoxalin-5-yl S 14144-(trifluoromethyl)phenyl 3-chloro-2-methylphenyl S 14154-(trifluoromethyl)phenyl 3-oxo-1,2,3,4- S tetrahydroisoquinolin-8-yl1416 4-(trifluoromethyl)phenyl 4-(methylamino)quinazolin- S 8-yl 14174-(trifluoromethyl)phenyl 4-aminoquinazolin-8-yl S 14184-(trifluoromethyl)phenyl 4-methylquinolin-8-yl S 14194-(trifluoromethyl)phenyl isoquinolin-5-yl S 14204-(trifluoromethyl)phenyl isoquinolin-8-yl S 14214-(trifluoromethyl)phenyl quinolin-5-yl S 1422 4-(trifluoromethyl)phenylquinolin-7-yl S 1423 4-(trifluoromethyl)phenyl quinolin-8-yl S 14244-(trifluoromethyl)piperidin-1-yl 2-amino-1,3-benzothiazol- S 4-yl 14254-acetylphenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl 14264-acetylphenyl 2-amino-1,3-benzothiazol- S 4-yl 14274-benzylpiperazin-1-yl 2-(acetylamino)-1,3- S benzothiazol-4-yl 14284-bromophenyl quinolin-7-yl S 1429 4-bromophenyl2-amino-1,3-benzothiazol- S 4-yl 1430 4-bromophenyl 2-(acetylamino)-1,3-S benzothiazol-4-yl 1431 4-chlorophenyl quinolin-7-yl S 14324′-fluoro-5-(trifluoromethyl)-1,1′-biphenyl- quinolin-7-yl S 2-yl 14334-fluorophenyl quinolin-7-yl S 1434 4-methylphenyl2-amino-1,3-benzothiazol- S 4-yl 1435 4-methylphenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 1436 4-phenylpiperazin-1-yl2-(acetylamino)-1,3- S benzothiazol-4-yl 14374-tert-butylcyclohex-1-en-1-yl 2-(acetylamino)-1,3- S benzothiazol-4-yl1438 4-tert-butylcyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- S 4-yl1439 4-tert-butylphenyl 2,3-dihydro-1,4- S benzodioxin-6-yl 14404-tert-butylphenyl 1H-1,2,3-benzotriazol-6-yl S 1441 4-tert-butylphenyl3-methoxyphenyl S 1442 4-tert-butylphenyl quinolin-7-yl S 14434-tert-butylphenyl 1,3-benzothiazol-6-yl S 1444 4-tert-butylphenylquinolin-7-yl S 1445 4-tert-butylphenyl 2-methyl-1,3-benzothiazol- S5-yl 1446 4-tert-butylphenyl 2-amino-1,3-benzothiazol- S 4-yl 14474-tert-butylphenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl

TABLE 2

Ex # R¹ R⁴ J 1448 {4-[1-(2-fluorophenyl)ethyl]piperazin-1-yl}2-(acetylamino)-1,3- NH benzothiazol-4-yl 1449{4-[ethyl(methyl)amino]phenyl} 2-(acetylamino)-1,3- NH benzothiazol-4-yl1450 1-benzofuran-5-yl quinolin-7-yl NH 14512-({[1-(tert-butoxycarbonyl)piperidin-3- 2-(acetylamino)-1,3- NHyl]carbonyl}amino)-4- benzothiazol-4-yl (trifluoromethyl)phenyl 14522-({[1-(tert-butoxycarbonyl)piperidin-4- 2-(acetylamino)-1,3- NHyl]methyl}amino)-4-(trifluoromethyl)phenyl benzothiazol-4-yl 14532-(2-pyrrolidin-1-ylethoxy)-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14542-(benzylamino)-4-(trifluoromethyl)phenyl quinolin-7-yl NH 14552-(benzyloxy)4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1456 2-(isonicotinoylamino)-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14572-(lactoylamino)-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- NH4-yl 1458 2-(methoxycarbonyl)-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 1459 2-(methoxymethoxy)-4-2-amino-1,3-benzothiazol- NH (trifluoromethyl)phenyl 4-yl 14602-(methylamino)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1461 2-(pentylamino)-4-(trifluoromethyl)phenylquinolin-7-yl NH 1462 2,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl2-(acetylamino)-1,3- NH benzothiazol-4-yl 14632,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl 2-amino-1,3-benzothiazol- NH4-yl 1464 2-[(2,2-dimethylpropanoyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14652-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14662-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-amino-1,3-benzothiazol- NH(trifluoromethyl)phenyl 4-yl 14672-[(3-piperidin-1-ylpropanoyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14682-[(4-tert-butylbenzyl)amino]-4- quinolin-7-yl NH(trifluoromethyl)phenyl 1469 2-[(cyclohexylacetyl)amino]-4-2-(acetylamino)-1,3- NH (trifluoromethyl)phenyl benzothiazol-4-yl 14702-[(cyclohexylcarbonyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14712-[(cyclohexylmethyl)amino]-4- 1,3-benzothiazol-6-yl NH(trifluoromethyl)phenyl 1472 2-[(cyclohexylmethyl)amino]-4-quinolin-7-yl NH (trifluoromethyl)phenyl 14732-[(cyclohexylmethyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14742-[(cyclohexylmethyl)amino]-6- quinolin-7-yl NH(trifluoromethyl)pyridin-3-yl 1475 2-[(cyclopentylacetyl)amino]-4-2-(acetylamino)-1,3- NH (trifluoromethyl)phenyl benzothiazol-4-yl 14762-[(cyclopropylcarbonyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14772-[(N,N-dimethylglycyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14782-[(piperidin-3-ylmethyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14792-[(pyridin-3-ylcarbonyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14802-[(pyridin-4-ylmethyl)amino]-4- quinolin-7-yl NH(trifluoromethyl)phenyl 1481 2-[(tert-butoxycarbonyl)amino]-4-quinolin-7-yl NH (trifluoromethyl)phenyl 14822-[(tert-butoxycarbonyl)amino]-4- 2-aminoquinolin-8-yl NH(trifluoromethyl)phenyl 1483 2-[(tert-butoxycarbonyl)amino]-4-2-(acetylamino)-1,3- NH (trifluoromethyl)phenyl benzothiazol-4-yl 14842-[2-(dimethylamino)ethoxy]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14852-{[(1-acetylpiperidin-4-yl)carbonyl]amino}- 2-(acetylamino)-1,3- NH4-(trifluoromethyl)phenyl benzothiazol-4-yl 14862-{[(1-methyl-1H-imidazol-5- 2-(acetylamino)-1,3- NHyl)carbonyl]amino}-4- benzothiazol-4-yl (trifluoromethyl)phenyl 14872-{[(1-methylpiperidin-4- 2-(acetylamino)-1,3- NH yl)carbonyl]amino}-4-benzothiazol-4-yl (trifluoromethyl)phenyl 14882-{[(1-propylpiperidin-4-yl)methyl]amino}- 2-(acetylamino)-1,3- NH4-(trifluoromethyl)phenyl benzothiazol-4-yl 14892-{[(4-{[tert-butyl(dimethyl)silyl]oxy}- 2-(acetylamino)-1,3- NHcyclohexyl)carbonyl]amino}-4- benzothiazol-4-yl (trifluoromethyl)phenyl1490 2-{[(4-hydroxycyclohexyl)carbonyl]amino}- 2-(acetylamino)-1,3- NH4-(trifluoromethyl)phenyl benzothiazol-4-yl 14912-{[hydroxy(phenyl)acetyl]amino}-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 14922-{[hydroxy(phenyl)acetyl]amino}-4- 2-amino-1,3-benzothiazol- NH(trifluoromethyl)phenyl 4-yl 1493 2-amino-4-(trifluoromethyl)phenylquinolin-7-yl NH 1494 2-amino-4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl NH 1495 2-amino-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 14962-bromo-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1497 2-chloro-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 14982-hydroxy-4-(trifluoromethyl)phenyl quinolin-7-yl NH 14992-hydroxy-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- NH 4-yl1500 2-hydroxy-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1501 2-iodo-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 1502 2-naphthyl quinolin-7-ylNH 1503 2-piperidin-1-yl-6-(trifluoromethyl)pyridin- quinolin-7-yl NH3-yl 1504 3-(trifluoromethoxy)phenyl quinolin-7-yl NH 15053-(trifluoromethoxy)phenyl 2-aminoquinolin-8-yl NH 15063,4-difluorophenyl quinolin-7-yl NH 1507 3-chloro-4-fluorophenylquinolin-7-yl NH 1508 3-fluoro-4-methylphenyl quinolin-7-yl NH 15094-(1-phenylethyl)piperazin-1-yl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1510 4-(2-fluorophenyl)piperazin-1-yl2-(acetylamino)-1,3- NH benzothiazol-4-yl 1511 4-(dimethylamino)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 15124-(trifluoromethoxy)phenyl quinolin-7-yl NH 15134-(trifluoromethoxy)phenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl1514 4-(trifluoromethyl)-2- 2-(acetylamino)-1,3- NH[(trifluoromethyl)sulfonyl]oxy}phenyl benzothiazol-4-yl 15154-(trifluoromethyl)-2-{[4- 2-(acetylamino)-1,3- NH(trifluoromethyl)benzoyl]amino}phenyl benzothiazol-4-yl 15164-(trifluoromethyl)cyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- NH 4-yl1517 4-(trifluoromethyl)cyclohex-1-en-1-yl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1518 4-(trifluoromethyl)phenyl 1,3-benzothiazol-4-ylNH 1519 4-(trifluoromethyl)phenyl 1,3-benzothiazol-5-yl NH 15204-(trifluoromethyl)phenyl 1H-benzimidazol-5-yl NH 15214-(trifluoromethyl)phenyl 1H-indazol-5-yl NH 15224-(trifluoromethyl)phenyl 1H-indol-4-yl NH 15234-(trifluoromethyl)phenyl 1H-indol-5-yl NH 15244-(trifluoromethyl)phenyl 1-methyl-2-oxo-1,2- NH dihydroquinoxalin-5-yl1525 4-(trifluoromethyl)phenyl 1-naphthyl NH 15264-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 15274-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NH benzoxazol-4-yl 15284-(trifluoromethyl)phenyl 2-(acetylamino)quinolin-8- NH yl 15294-(trifluoromethyl)phenyl 2-(aminocarbonyl)-1,3- NH benzothiazol-4-yl1530 4-(trifluoromethyl)phenyl 2-(hydroxymethyl)-2,3- NH dihydro-1,4-benzodioxin-6-yl 1531 4-(trifluoromethyl)phenyl2-(lactoylamino)-1,3- NH benzothiazol-4-yl 15324-(trifluoromethyl)phenyl 2-(methylamino)quinolin-8- NH yl 15334-(trifluoromethyl)phenyl 2-(pyridin-2-ylamino)-1,3- NHbenzothiazol-4-yl 1534 4-(trifluoromethyl)phenyl 2,3-dihydro-1,4- NHbenzodioxin-6-yl 1535 4-(trifluoromethyl)phenyl2,3-dimethyl-1H-indol-6-yl NH 1536 4-(trifluoromethyl)phenyl2,6-diamino-1,3- NH benzothiazol-4-yl 1537 4-(trifluoromethyl)phenyl2-amino-1,3-benzothiazol- NH 4-yl 1538 4-(trifluoromethyl)phenyl2-aminoimidazo[1,2- NH a]pyridin-8-yl 1539 4-(trifluoromethyl)phenyl2-aminoquinazolin-8-yl NH 1540 4-(trifluoromethyl)phenyl2-aminoquinolin-7-yl NH 1541 4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl NH 1542 4-(trifluoromethyl)phenyl2-aminoquinoxalin-5-yl NH 1543 4-(trifluoromethyl)phenyl2-chloro-1,3-benzothiazol- NH 4-yl 1544 4-(trifluoromethyl)phenyl2-chloroquinolin-8-yl NH 1545 4-(trifluoromethyl)phenyl 2-hydroxy-1,3-NH benzothiazol-4-yl 1546 4-(trifluoromethyl)phenyl 2-hydroxy-4- NHmethylquinolin-7-yl 1547 4-(trifluoromethyl)phenyl2-hydroxyquinolin-7-yl NH 1548 4-(trifluoromethyl)phenyl2-hydroxyquinoxalin-5-yl NH 1549 4-(trifluoromethyl)phenyl2-methyl-1,3-benzothiazol- NH 5-yl 1550 4-(trifluoromethyl)phenyl2-naphthyl NH 1551 4-(trifluoromethyl)phenyl 2-oxo-1,2,3,4- NHtetrahydroquinolin-7-yl 1552 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4-tetra- NH hydroquinoxalin-5-yl 15534-(trifluoromethyl)phenyl 2-pyridin-4-yl-1,3- NH benzothiazol-4-yl 15544-(trifluoromethyl)phenyl 3-( 1-hydroxy-1-methy- NH lethyl)quinolin-7-yl1555 4-(trifluoromethyl)phenyl 3-( 1-hydroxyethyl)quinolin- NH 7-yl 15564-(trifluoromethyl)phenyl 3-(hydroxymethyl)-1,2,3,4- NHtetrahydroquinolin-7-yl 1557 4-(trifluoromethyl)phenyl3-(hydroxymethyl)-2-oxo- NH 1,2,3,4-tetrahydroquinolin- 7-yl 15584-(trifluoromethyl)phenyl 3-(hydroxymethyl)quinolin- NH 7-yl 15594-(trifluoromethyl)phenyl 3-(methoxycarbonyl)- NH quinolin-7-yl 15604-(trifluoromethyl)phenyl 3,4-dimethylphenyl NH 15614-(trifluoromethyl)phenyl 3-amino-2-oxo-1,2- NH dihydroquinoxalin-5-yl1562 4-(trifluoromethyl)phenyl 3-aminoquinoxalin-5-yl NH 15634-(trifluoromethyl)phenyl 3-chloro-2-methylphenyl NH 15644-(trifluoromethyl)phenyl 3-oxo-1,2,3,4-tetrahydro- NH isoquinolin-8-yl1565 4-(trifluoromerhyl)phenyl 4-(methylamino)quinazolin- NH 8-yl 15664-(trifluoromethyl)phenyl 4-aminoquinazolin-8-yl NH 15674-(trifluoromethyl)phenyl 4-methylquinolin-8-yl NH 15684-(trifluoromethyl)phenyl isoquinolin-5-yl NH 15694-(trifluoromethyl)phenyl isoquinolin-8-yl NH 15704-(trifluoromethyl)phenyl quinolin-5-yl NH 15714-(trifluoromethyl)phenyl quinolin-7-yl NH 15724-(trifluoromethyl)phenyl quinolin-8-yl NH 15734-(trifluoromethyl)piperidin-1-yl 2-amino-1,3-benzothiazol- NH 4-yl 15744-acetylphenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 15754-acetylphenyl 2-amino-1,3-benzothiazol- NH 4-yl 15764-benzylpiperazin-1-yl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 15774-bromophenyl quinolin-7-yl NH 1578 4-bromophenyl2-amino-1,3-benzothiazol- NH 4-yl 1579 4-bromophenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 1580 4-chlorophenylquinolin-7-yl NH 1581 4′-fluoro-5-(trifluoromethyl)-1,1′-biphenyl-2-quinolin-7-yl NH yl 1582 4-fluorophenyl quinolin-7-yl NH 15834-methylphenyl 2-amino-1,3-benzothiazol- NH 4-yl 1584 4-methylphenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 1585 4-phenylpiperazin-1-yl2-(acetylamino)-1,3- NH benzothiazol-4-yl 15864-tert-butylcyclohex-1-en-1-yl 2-(acetylamino)-1,3- NH benzothiazol-4-yl1587 4-tert-butylcyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- NH 4-yl1588 4-tert-butylphenyl 2,3-dihydro-1,4- NH benzodioxin-6-yl 15894-tert-butylphenyl 1H-1,2,3-benzotriazol-6-yl NH 1590 4-tert-butylphenyl3-methoxyphenyl NH 1591 4-tert-butylphenyl quinolin-7-yl NH 15924-tert-butylphenyl 1,3-benzothiazol-6-yl NH 1593 4-tert-butylphenylquinolin-7-yl NH 1594 4-tert-butylphenyl 2-methyl-1,3-benzothiazol- NH5-yl 1595 4-tert-butylphenyl 2-amino-1,3-benzothiazol- NH 4-yl 15964-tert-butylphenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 1597{4-[1-(2-fluorophenyl)ethyl]piperazin-1-yl} 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1598 {4-[ethyl(methyl)amino]phenyl}2-(acetylamino)-1,3- O benzothiazol-4-yl 1599 1-benzofuran-5-ylquinolin-7-yl O 1600 2-({[1-(tert-butoxycarbonyl)piperidin-3-2-(acetylamino)-1,3- O yl]carbonyl}amino)-4- benzothiazol-4-yl(trifluoromethyl)phenyl 1601 2-({[1-(tert-butoxycarbonyl)piperidin-4-2-(acetylamino)-1,3- O yl]methyl}amino)-4-(trifluoromethyl)phenylbenzothiazol-4-yl 1602 2-(2-pyrrolidin-1-ylethoxy)-4-2-(acetylamino)-1,3- O (trifluoromethyl)phenyl benzothiazol-4-yl 16032-(benzylamino)-4-(trifluoromethyl)phenyl quinolin-7-yl O 16042-(benzyloxy)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1605 2-(isonicotinoylamino)-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16062-(lactoylamino)-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- O4-yl 1607 2-(methoxycarbonyl)-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 1608 2-(methoxymethoxy)-4-2-amino-1,3-benzothiazol- O (trifluoromethyl)phenyl 4-yl 16092-(methylamino)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1610 2-(pentylamino)4-(trifluoromethyl)phenylquinolin-7-yl O 1611 2,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl2-(acetylamino)-1,3- O benzothiazol-4-yl 16122,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl 2-amino-1,3-benzothiazol- O4-yl 1613 2-[(2,2-dimethylpropanoyl)amino]4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16142-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16152-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-amino-1,3-benzothiazol- O(trifluoromethyl)phenyl 4-yl 16162-[(3-piperidin-1-ylpropanoyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16172-[(4-tert-butylbenzyl)amino]-4- quinolin-7-yl O (trifluoromethyl)phenyl1618 2-[(cyclohexylacetyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16192-[(cyclohexylcarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16202-[(cyclohexylmethyl)amino]-4- 1,3-benzothiazol-6-yl O(trifluoromethyl)phenyl 1621 2-[(cyclohexylmethyl)amino]-4-quinolin-7-yl O (trifluoromethyl)phenyl 16222-[(cyclohexylmethyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16232-[(cyclohexylmethyl)amino]-6- quinolin-7-yl O(trifluoromethyl)pyridin-3-yl 1624 2-[(cyclopentylacetyl)amino]-4-2-(acetylamino)-1,3- O (trifluoromethyl)phenyl benzothiazol-4-yl 16252-[(cyclopropylcarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16262-[(N,N-dimethylglycyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16272-[(piperidin-3-ylmethyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16282-[(pyridin-3-ylcarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16292-[(pyridin-4-ylmethyl)amino]-4- quinolin-7-yl O (trifluoromethyl)phenyl1630 2-[(tert-butoxycarbonyl)amino]-4- quinolin-7-yl O(trifluoromethyl)phenyl 1631 2-[(tert-butoxycarbonyl)amino]-4-2-aminoquinolin-8-yl O (trifluoromethyl)phenyl 16322-[(tert-butoxycarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16332-[2-(dimethylamino)ethoxy]- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16342-{[(1-acetylpiperidin-4-yl)carbonyl]amino}- 2-(acetylamino)-1,3- O4-(trifluoromethyl)phenyl benzothiazol-4-yl 16352-{[(1-methyl-1H-imidazol-5- 2-(acetylamino)-1,3- Oyl)carbonyl]amino}-4- benzothiazol-4-yl (trifluoromethyl)phenyl 16362-{[(1-methylpiperidin-4- 2-(acetylamino)-1,3- O yl)carbonyl]amino)-4-benzothiazol-4-yl (trifluoromethyl)phenyl 16372-{[(1-propylpiperidin-4-yl)methyl]amino)- 2-(acetylamino)-1,3- O4-(trifluoromethyl)phenyl benzothiazol-4-yl 16382-{[(4-{[tert-butyl(dimethyl)silyl]oxy}- 2-(acetylamino)-1,3- Ocyclohexyl)carbonyl]amino}-4- benzothiazol-4-yl (trifluoromethyl)phenyl1639 2-{[(4-hydroxycyclohexyl)carbonyl]amino}- 2-(acetylamino)-1,3- O4-(trifluoromethyl)phenyl benzothiazol-4-yl 16402-{[hydroxy(phenyl)acetyl]amino}-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 16412-{[hydroxy(phenyl)acetyl]amino}-4- 2-amino-1,3-benzothiazol- O(trifluoromethyl)phenyl 4-yl 1642 2-amino-4-(trifluoromethyl)phenylquinolin-7-yl O 1643 2-amino-4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl O 1644 2-amino-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 16452-bromo-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1646 2-chloro-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 16472-hydroxy-4-(trifluoromethyl)phenyl quinolin-7-yl O 16482-hydroxy-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- O 4-yl1649 2-hydroxy-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1650 2-iodo-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 1651 2-naphthyl quinolin-7-yl O1652 2-piperidin-1-yl-6-(trifluoromethyl)pyridin- quinolin-7-yl O 3-yl1653 3-(trifluoromethoxy)phenyl quinolin-7-yl O 16543-(trifluoromethoxy)phenyl 2-aminoquinolin-8-yl O 16553,4-difluorophenylquinolin-7-yl O 1656 3-chloro-4-fluorophenylquinolin-7-yl O 1657 3-fluoro-4-methylphenyl quinolin-7-yl O 16584-(1-phenylethyl)piperazin-1-yl 2-(acetylamino)-1,3- O benzothiazol-4-yl1659 4-(2-fluorophenyl)piperazin-1-yl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1660 4-(dimethylamino)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1661 4-(trifluoromethoxy)phenyl quinolin-7-yl O 16624-(trifluoromethoxy)phenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 16634-(trifluoromethyl)-2- 2-(acetylamino)-1,3- O[(trifluoromethyl)sulfonyl]oxy}phenyl benzothiazol-4-yl 16644-(trifluoromethyl)-2-{[4- 2-(acetylamino)-1,3- O(trifluoromethyl)benzoyl]amino}phenyl benzothiazol-4-yl 16654-(trifluoromethyl)cyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- O 4-yl1666 4-(trifluoromethyl)cyclohex-1-en-1-yl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 1667 4-(trifluoromethyl)phenyl 1,3-benzothiazol-4-yl O1668 4-(trifluoromethyl)phenyl 1,3-benzothiazol-5-yl O 16694-(trifluoromethyl)phenyl 1H-benzimidazol-5-yl O 16704-(trifluoromethyl)phenyl 1H-indazol-5-yl O 16714-(trifluoromethyl)phenyl 1H-indol-4-yl O 1672 4-(trifluoromethyl)phenyl1H-indol-5-yl O 1673 4-(trifluoromethyl)phenyl 1-methyl-2-oxo-1,2- Odihydroquinoxalin-5-yl 1674 4-(trifluoromethyl)phenyl 1-naphthyl O 16754-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 16764-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- O benzoxazol-4-yl 16774-(trifluoromethyl)phenyl 2-(acetylamino)quinolin-8- O yl 16784-(trifluoromethyl)phenyl 2-(aminocarbonyl)-1,3- O benzothiazol-4-yl1679 4-(trifluoromethyl)phenyl 2-(hydroxymethyl)-2,3- Odihydro-1,4-benzodioxin-6-yl 1680 4-(trifluoromethyl)phenyl2-(lactoylamino)-1,3- O benzothiazol-4-yl 1681 4-(trifluoromethyl)phenyl2-(methylamino)quinolin-8- O 1682 4-(trifluoromethyl)phenyl2-(pyridin-2-ylamino)-1,3- O benzothiazol-4-yl 16834-(trifluoromethyl)phenyl 2,3-dihydro-1,4- O benzodioxin-6-yl 16844-(trifluoromethyl)phenyl 2,3-dimethyl-1H-indol-6-yl O 16854-(trifluoromethyl)phenyl 2,6-diamino-1,3- O benzothiazol-4-yl 16864-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- O 4-yl 16874-(trifluoromethyl)phenyl 2-aminoimidazo[1,2- O a]pyridin-8-yl 16884-(trifluoromethyl)phenyl 2-aminoquinazolin-8-yl O 16894-(trifluoromethyl)phenyl 2-aminoquinolin-7-yl O 16904-(trifluoromethyl)phenyl 2-aminoquinolin-8-yl O 16914-(trifluoromethyl)phenyl 2-aminoquinoxalin-5-yl O 16924-(trifluoromethyl)phenyl 2-chloro-1,3-benzothiazol- O 4-yl 16934-(trifluoromethyl)phenyl 2-chloroquinolin-8-yl O 16944-(trifluoromethyl)phenyl 2-hydroxy-1,3- O benzothiazol-4-yl 16954-(trifluoromethyl)phenyl 2-hydroxy-4- O methylquinolin-7-yl 16964-(trifluoromethyl)phenyl 2-hydroxyquinolin-7-yl O 16974-(trifluoromethyl)phenyl 2-hydroxyquinoxalin-5-yl O 16984-(trifluoromethyl)phenyl 2-methyl-1,3-benzothiazol- O 5-yl 16994-(trifluoromethyl)phenyl 2-naphthyl O 1700 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- O tetrahydroquinolin-7-yl 1701 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- O tetrahydroquinoxalin-5-yl 17024-(trifluoromethyl)phenyl 2-pyridin-4-yl-1,3- O benzothiazol-4-yl 17034-(trifluoromethyl)phenyl 3-(1-hydroxy-1-methyl- O ethyl)quinolin-7-yl1704 4-(trifluoromethyl)phenyl 3-(1-hydroxyethyl)quinolin- O 7-yl 17054-(trifluoromethyl)phenyl 3-(hydroxymethyl)-1,2,3,4- Otetrahydroquinolin-7-yl 1706 4-(trifluoromethyl)phenyl3-(hydroxymethyl)-2-oxo- O 1,2,3,4-tetrahydroquinolin- 7-yl 17074-(trifluoromethyl)phenyl 3-(hydroxymethyl)quinolin- O 7-yl 17084-(trifluoromethyl)phenyl 3-(methoxycarbonyl)- O quinolin-7-yl 17094-(trifluoromethyl)phenyl 3,4-dimethylphenyl O 17104-(trifluoromethyl)phenyl 3-amino-2-oxo-1,2- O dihydroquinoxalin-5-yl1711 4-(trifluoromethyl)phenyl 3-aminoquinoxalin-5-yl O 17124-(trifluoromethyl)phenyl 3-chloro-2-methylphenyl O 17134-(trifluoromethyl)phenyl 3-oxo-1,2,3,4-tetrahydro- O isoquinolin-8-yl1714 4-(trifluoromethyl)phenyl 4-(methylamino)quinazolin- O 8-yl 17154-(trifluoromethyl)phenyl 4-aminoquinazolin-8-yl O 17164-(trifluoromethyl)phenyl 4-methylquinolin-8-yl O 17174-(trifluoromethyl)phenyl isoquinolin-5-yl O 17184-(trifluoromethyl)phenyl isoquinolin-8-yl O 17194-(trifluoromethyl)phenyl quinolin-5-yl O 1720 4-(trifluoromethyl)phenylquinolin-7-yl O 1721 4-(trifluoromethyl)phenyl quinolin-8-yl O 17224-(trifluoromethyl)piperidin-1-yl 2-amino-1,3-benzothiazol- O 4-yl 17234-acetylphenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 17244-acetylphenyl 2-amino-1,3-benzothiazol- O 4-yl 17254-benzylpiperazin-1-yl 2-(acetylamino)-1,3- O benzothiazol-4-yl 17264-bromophenyl quinolin-7-yl O 1727 4-bromophenyl2-amino-1,3-benzothiazol- O 4-yl 1728 4-bromophenyl 2-(acetylamino)-1,3-O benzothiazol-4-yl 1729 4-chlorophenyl quinolin-7-yl O 17304′-fluoro-5-(trifluoromethyl)-1,1′-biphenyl-2- quinolin-7-yl O yl 17314-fluorophenyl quinolin-7-yl O 1732 4-methylphenyl2-amino-1,3-benzothiazol- O 4-yl 1733 4-methylphenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 1734 4-phenylpiperazin-1-yl2-(acetylamino)-1,3- O benzothiazol-4-yl 17354-tert-butylcyclohex-1-en-1-yl 2-(acetylamino)-1,3- O benzothiazol-4-yl1736 4-tert-butylcyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- O 4-yl1737 4-tert-butylphenyl 2,3-dihydro-1,4- O benzodioxin-6-yl 17384-tert-butylphenyl 1H-1,2,3-benzotriazol-6-yl O 1739 4-tert-butylphenyl3-methoxyphenyl O 1740 4-tert-butylphenyl quinolin-7-yl O 17414-tert-butylphenyl 1,3-benzothiazol-6-yl O 1742 4-tert-butylphenylquinolin-7-yl O 1743 4-tert-butylphenyl 2-methyl-1,3-benzothiazol- O5-yl 1744 4-tert-butylphenyl 2-amino-1,3-benzothiazol- O 4-yl 17454-tert-butylphenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 1746{4-[1-(2-fluorophenyl)ethyl]piperazin-1-yl} 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1747 {4-[ethyl(methyl)amino]phenyl}2-(acetylamino)-1,3- S benzothiazol-4-yl 1748 1-benzofuran-5-ylquinolin-7-yl S 1749 2-({[1-(tert-butoxycarbonyl)piperidin-3-2-(acetylamino)-1,3- S yl]carbonyl}amino)-4- benzothiazol-4-yl(trifluoromethyl)phenyl 1750 2-({[1-(tert-butoxycarbonyl)piperidin-4-2-(acetylamino)-1,3- S yl]methyl}amino)-4-(trifluoromethyl)phenylbenzothiazol-4-yl 1751 2-(2-pyrrolidin-1-ylethoxy)-4-2-(acetylamino)-1,3- S (trifluoromethyl)phenyl benzothiazol-4-yl 17522-(benzylamino)-4-(trifluoromethyl)phenyl quinolin-7-yl S 17532-(benzyloxy)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1754 2-(isonicotinoylamino)-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 17552-(lactoylamino)-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- S4-yl 1756 2-(methoxycarbonyl)-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 1757 2-(methoxymethoxy)-4-2-amino-1,3-benzothiazol- S (trifluoromethyl)phenyl 4-yl 17582-(methylamino)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1759 2-(pentylamino)-4-(trifluoromethyl)phenylquinolin-7-yl S 1760 2,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl2-(acetylamino)-1,3- S benzothiazol-4-yl 17612,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl 2-amino-1,3-benzothiazol- S4-yl 1762 2-[(2,2-dimethylpropanoyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 17632-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 17642-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-amino-1,3-benzothiazol- S(trifluoromethyl)phenyl 4-yl 17652-[(3-piperidin-1-ylpropanoyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 17662-[(4-tert-butylbenzyl)amino]-4- quinolin-7-yl S (trifluoromethyl)phenyl1767 2-[(cyclohexylacetyl)amino]-4- 2-(acetylamino)-1,3- 5(trifluoromethyl)phenyl benzothiazol-4-yl 17682-[(cyclohexylcarbonyl)amino]-4- 2-(acetylamino)-1,3- 5(trifluoromethyl)phenyl benzothiazol-4-yl 17692-[(cyclohexylmethyl)amino]-4- 1,3-benzothiazol-6-yl S(trifluoromethyl)phenyl 1770 2-[(cyclohexylmethyl)amino]-4-quinolin-7-yl S (trifluoromethyl)phenyl 17712-[(cyclohexylmethyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 17722-[(cyclohexylmethyl)amino]-6- quinolin-7-yl S(trifluoromethyl)pyridin-3-yl 1773 2-[(cyclopentylacetyl)amino]-4-2-(acetylamino)-1,3- S (trifluoromethyl)phenyl benzothiazol-4-yl 17742-[(cyclopropylcarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 17752-[(N,N-dimethylglycyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 17762-[(piperidin-3-ylmethyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 17772-[(pyridin-3-ylcarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 17782-[(pyridin-4-ylmethyl)amino]-4- quinolin-7-yl S (trifluoromethyl)phenyl1779 2-[(tert-butoxycarbonyl)amino]-4- quinolin-7-yl S(trifluoromethyl)phenyl 1780 2-[(tert-butoxycarbonyl)amino]-4-2-aminoquinolin-8-yl S (trifluoromethyl)phenyl 17812-[(tert-butoxycarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 17822-[2-(dimethylamino)ethoxy]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 17832-{[(1-acetylpiperidin-4-yl)carbonyl]amino}- 2-(acetylamino)-1,3- S4-(trifluoromethyl)phenyl benzothiazol-4-yl 17842-{[(1-methyl-1H-imidazol-5- 2-(acetylamino)-1,3- Syl)carbonyl]amino}-4- benzothiazol-4-yl (trifluoromethyl)phenyl 17852-{[(1-methylpiperidin-4- 2-(acetylamino)-1,3- S yl)carbonyl]amino}-4-benzothiazol-4-yl (trifluoromethyl)phenyl 17862-{[(1-propylpiperidin-4-yl)methyl]amino}- 2-(acetylamino)-1,3- S4-(trifluoromethyl)phenyl benzothiazol-4-yl 1787 2-{[(4-{[tert-2-(acetylamino)-1,3- S butyl(dimethyl)silyl]oxy}cyclohexyl)benzothiazol-4-yl carbonyl]amino}-4-(trifluoromethyl)phenyl 17882-{[(4-hydroxycyclohexyl)carbonyl]amino}- 2-(acetylamino)-1,3- S4-(trifluoromethyl)phenyl benzothiazol-4-yl 17892-{[hydroxy(phenyl)acetyl]amino}-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 17902-{[hydroxy(phenyl)acetyl]amino}-4- 2-amino-1,3-benzothiazol- S(trifluoromethyl)phenyl 4-yl 1791 2-amino-4-(trifluoromethyl)phenylquinolin-7-yl S 1792 2-amino-4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl S 1793 2-amino-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 17942-bromo-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1795 2-chloro-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 17962-hydroxy-4-(trifluoromethyl)phenyl quinolin-7-yl S 17972-hydroxy-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- S 4-yl1798 2-hydroxy-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1799 2-iodo-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 1800 2-naphthyl quinolin-7-yl S1801 2-piperidin-1-yl-6-(trifluoromethyl)pyridin- quinolin-7-yl S 3-yl1802 3-(trifluoromethoxy)phenyl quinolin-7-yl S 18033-(trifluoromethoxy)phenyl 2-aminoquinolin-8-yl S 18043,4-difluorophenyl quinolin-7-yl S 1805 3-chloro-4-fluorophenylquinolin-7-yl S 1806 3-fluoro-4-methylphenyl quinolin-7-yl S 18074-(1-phenylethyl)piperazin-1-yl 2-(acetylamino)-1,3- S benzothiazol-4-yl1808 4-(2-fluorophenyl)piperazin-1-yl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1809 4-(dimethylamino)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1810 4-(trifluoromethoxy)phenyl quinolin-7-yl S 18114-(trifluoromethoxy)phenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl 18124-(trifluoromethyl)-2- 2-(acetylamino)-1,3- S{[(trifluoromethyl)sulfonyl]oxy}phenyl benzothiazol-4-yl 18134-(trifluoromethyl)-2-{[4- 2-(acetylamino)-1,3- S(trifluoromethyl)benzoyl]amino}phenyl benzothiazol-4-yl 18144-(trifluoromethyl)cyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- S 4-yl1815 4-(trifluoromethyl)cyclohex-1-en-1-yl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 1816 4-(trifluoromethyl)phenyl 1,3-benzothiazol-4-yl S1817 4-(trifluoromethyl)phenyl 1,3-benzothiazol-5-yl S 18184-(trifluoromethyl)phenyl 1H-benzimidazol-5-yl S 18194-(trifluoromethyl)phenyl 1H-indazol-5-yl S 18204-(trifluoromethyl)phenyl 1H-indol-4-yl S 1821 4-(trifluoromethyl)phenyl1H-indol-5-yl S 1822 4-(trifluoromethyl)phenyl 1-methyl-2-oxo-1,2- Sdihydroquinoxalin-5-yl 1823 4-(trifluoromethyl)phenyl 1-naphthyl S 18244-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl 18254-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- S benzoxazol-4-yl 18264-(trifluoromethyl)phenyl 2-(acetylamino)quinolin-8-yl S 18274-(trifluoromethyl)phenyl 2-(aminocarbonyl)-1,3- S benzothiazol-4-yl1828 4-(trifluoromethyl)phenyl 2-(hydroxymethyl)-2,3- Sdihydro-1,4-benzodioxin-6-yl 1829 4-(trifluoromethyl)phenyl2-(lactoylamino)-1,3- S benzothiazol-4-yl 1830 4-(trifluoromethyl)phenyl2-(methylamino)quinolin-8- S yl 1831 4-(trifluoromethyl)phenyl2-(pyridin-2-ylamino)-1,3- S benzothiazol-4-yl 18324-(trifluoromethyl)phenyl 2,3-dihydro-1,4- S benzodioxin-6-yl 18334-(trifluoromethyl)phenyl 2,3-dimethyl-1H-indol-6-yl S 18344-(trifluoromethyl)phenyl 2,6-diamino-1,3- S benzothiazol-4-yl 18354-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- S 4-yl 18364-(trifluoromethyl)phenyl 2-aminoimidazo[1,2- S a]pyridin-8-yl 18374-(trifluoromethyl)phenyl 2-aminoquinazolin-8-yl S 18384-(trifluoromethyl)phenyl 2-aminoquinolin-7-yl S 18394-(trifluoromethyl)phenyl 2-aminoquinolin-8-yl S 18404-(trifluoromethyl)phenyl 2-aminoquinoxalin-5-yl S 18414-(trifluoromethyl)phenyl 2-chioro-1,3-benzothiazol- S 4-yl 18424-(trifluoromethyl)phenyl 2-chloroquinolin-8-yl S 18434-(trifluoromethyl)phenyl 2-hydroxy-1,3- S benzothiazol-4-yl 18444-(trifluoromethyl)phenyl 2-hydroxy-4- S methylquinolin-7-yl 18454-(trifluoromethyl)phenyl 2-hydroxyquinolin-7-yl S 18464-(trifluoromethyl)phenyl 2-hydroxyquinoxalin-5-yl S 18474-(trifluoromethyl)phenyl 2-methyl-1,3-benzothiazol- S 5-yl 18484-(trifluoromethyl)phenyl 2-naphthyl S 1849 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- S tetrahydroquinolin-7-yl 1850 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4-tetra- S hydroquinoxalin-5-yl 18514-(trifluoromethyl)phenyl 2-pyridin-4-yl-1,3- S benzothiazol-4-yl 18524-(trifluoromethyl)phenyl 3-(1-hydroxy-1-methyl- S ethyl)quinolin-7-yl1853 4-(trifluoromethyl)phenyl 3-(1-hydroxyethyl)quinolin- S 7-yl 18544-(trifluoromethyl)phenyl 3-(hydroxymethyl)-1,2,3,4- Stetrahydroquinolin-7-yl 1855 4-(trifluoromethyl)phenyl3-(hydroxymethyl)-2-oxo- S 1,2,3,4-tetrahydroquinolin- 7-yl 18564-(trifluoromethyl)phenyl 3-(hydroxymethyl)quinolin- S 7-yl 18574-(trifluoromethyl)phenyl 3-(methoxycarbonyl)- S quinolin-7-yl 18584-(trifluoromethyl)phenyl 3,4-dimethylphenyl S 18594-(trifluoromethyl)phenyl 3-amino-2-oxo-1,2- S dihydroquinoxalin-5-yl1860 4-(trifluoromethyl)phenyl 3-aminoquinoxalin-5-yl S 18614-(trifluoromethyl)phenyl 3-chloro-2-methylphenyl S 18624-(trifluoromethyl)phenyl 3-oxo-1,2,3,4-tetra- S hydroisoquinolin-8-yl1863 4-(trifluoromethyl)phenyl 4-(methylamino)quinazolin- S 8-yl 18644-(trifluoromethyl)phenyl 4-aminoquinazolin-8-yl S 18654-(trifluoromethyl)phenyl 4-methylquinolin-8-yl S 18664-(trifluoromethyl)phenyl isoquinolin-5-yl S 18674-(trifluoromethyl)phenyl isoquinolin-8-yl S 18684-(trifluoromethyl)phenyl quinolin-5-yl S 1869 4-(trifluoromethyl)phenylquinolin-7-yl S 1870 4-(trifluoromethyl)phenyl quinolin-8-yl S 18714-(trifluoromethyl)piperidin-1-yl 2-amino-1,3-benzothiazol- S 4-yl 18724-acetylphenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl 18734-acetylphenyl 2-amino-1,3-benzothiazol- S 4-yl 18744-benzylpiperazin-1-yl 2-(acetylamino)-1,3- S benzothiazol-4-yl 18754-bromophenyl quinolin-7-yl S 1876 4-bromophenyl2-amino-1,3-benzothiazol- S 4-yl 1877 4-bromophenyl 2-(acetylamino)-1,3-S benzothiazol-4-yl 1878 4-chlorophenyl quinolin-7-yl S 18794′-fluoro-5-(trifluoromethyl)-1,1′-biphenyl-2- quinolin-7-yl S yl 18804-fluorophenyl quinolin-7-yl S 1881 4-methylphenyl2-amino-1,3-benzothiazol- S 4-yl 1882 4-methylphenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 1883 4-phenylpiperazin-1-yl2-(acetylamino)-1,3- S benzothiazol-4-yl 18844-tert-butylcyclohex-1-en-1-yl 2-(acetylamino)-1,3- S benzothiazol-4-yl1885 4-tert-butylcyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- S 4-yl1886 4-tert-butylphenyl 2,3-dihydro-1,4- S benzodioxin-6-yl 18874-tert-butylphenyl 1H-1,2,3-benzotriazol-6-yl S 1888 4-tert-butylphenyl3-methoxyphenyl S 1889 4-tert-butylphenyl quinolin-7-yl S 18904-tert-butylphenyl 1,3-benzothiazol-6-yl S 1891 4-tert-butylphenylquinolin-7-yl S 1892 4-tert-butylphenyl 2-methyl-1,3-benzothiazol- S5-yl 1893 4-tert-butylphenyl 2-amino-1,3-benzothiazol- S 4-yl 18944-tert-butylphenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl

TABLE 3

Ex # R¹ R⁴ J 1895 {4-[1-(2-fluorophenyl)ethyl]piperazin-1-yl}2-(acetylamino)-1,3- NH benzothiazol-4-yl 1896{4-[ethyl(methyl)amino]phenyl} 2-(acetylamino)-1,3- NH benzothiazol-4-yl1897 1-benzofuran-5-yl quinolin-7-yl NH 18982-({[1-(tert-butoxycarbonyl)piperidin-3- 2-(acetylamino)-1,3- NHyl]carbonyl}amino)-4- benzothiazol-4-yl (trifluoromethyl)phenyl 18992-({[1-(tert-butoxycarbonyl)piperidin-4- 2-(acetylamino)-1,3- NHyl]methyl}amino)-4-(trifluoromethyl)phenyl benzothiazol-4-yl 19002-(2-pyrrolidin-1-ylethoxy)-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 19012-(benzylamino)-4-(trifluoromethyl)phenyl quinolin-7-yl NH 19022-(benzyloxy)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1903 2-(isonicotinoylamino)-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol4-yl 19042-(lactoylamino)-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- NH4-yl 1905 2-(methoxycarbonyl)-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 1906 2-(methoxymethoxy)-4-2-amino-1,3-benzothiazol- NH (trifluoromethyl)phenyl 4-yl 19072-(methylan-uno)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1908 2-(pentylamino)-4-(trifluoromethyl)phenylquinolin-7-yl NH 1909 2,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl2-(acetylamino)-1,3- NH benzothiazol-4-yl 19102,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl 2-amino-1,3-benzothiazol- NH4-yl 1911 2-[(2,2-dimethylpropanoyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 19122-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 19132-[(2-hydroxy-2-merhylpropanoyl)amino]-4- 2-amino-1,3-benzothiazol- NH(trifluoromethyl)phenyl 4-yl 19142-[(3-piperidin-1-ylpropanoyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 19152-[(4-tert-butylbenzyl)amino]-4- quinolin-7-yl NH(trifluoromethyl)phenyl 1916 2-[(cyclohexylacetyl)amino]-4-2-(acetylamino)-1,3- NH (trifluoromethyl)phenyl benzothiazol-4-yl 19172-[(cyclohexylcarbonyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 19182-[(cyclohexylmethyl)amino]-4- 1,3-benzothiazol-6-yl NH(trifluoromethyl)phenyl 1919 2-[(cyclohexylmethyl)amino]-4-quinolin-7-yl NH (trifluoromethyl)phenyl 19202-[(cyclohexylmethyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 19212-[(cyclohexylmethyl)amino]-6-quinolin-7-yl NH(trifluoromethyl)pyridin-3-yl 1922 2-[(cyclopentylacetyl)amino]-4-2-(acetylamino)-1,3- NH (trifluoromethyl)phenyl benzothiazol-4-yl 19232-[(cyclopropylcarbonyl)-amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 19242-[(N,N-dimethylglycyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 19252-[(piperidin-3-ylmethyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 19262-[(pyridin-3-ylcarbonyl)amino]-4- 2-(acetylamino)-1,3- NH(tnfluoromethyl)phenyl benzothiazol-4-yl 19272-[(pyridin-4-ylmethyl)amino]-4- quinolin-7-yl NH(trifluoromethyl)phenyl 1928 2-[(tert-butoxycarbonyl)amino]-4-quinolin-7-yl NH (trifluoromethyl)phenyl 19292-[(tert-butoxycarbonyl)amino]-4- 2-aminoquinolin-8-yl NH(trifluoromethyl)phenyl 1930 2-[(tert-butoxycarbonyl)amino]-2-(acetylamino)-1,3- NH (trifluoromethyl)phenyl benzothiazol-4-yl 19312-[2-(dimethylamino)ethoxy]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 19322-{[(1-acetylpiperidin-4-yl)carbonyl]amino}- 2-(acetylamino)-1,3- NH4-(trifluoromethyl)phenyl benzothiazol-4-yl 19332-{[(1-methyl-1H-imidazol-5- 2-(acetylamino)-1,3- NH yl)carbonyl]amino1-4- benzothiazol-4-yl (trifluoromethyl)phenyl 1934 2-{[(1-methylpiperidin-4- 2-(acetylamino)-1,3- NH yl)carbonyl]amino}-4-benzothiazol-4-yl (trifluoromethyl)phenyl 1935 2-{[(1-propylpiperidin-4-yl)methyl]amino}- 2-(acetylamino)-1,3- NH4-(trifluoromethyl)phenyl benzothiazol-4-yl 1936 2-{[(4-{[tert-2-(acetylamino)-1,3- NH butyl(dimethyl)silyl[oxy}cyclohexyl)carbonybenzothiazol-4-yl l]amino}-4- (trifluoromethyl)phenyl 19372-{[(4-hydroxycyclohexyl)carbonyl]amino}- 2-(acetylamino)-1,3- NH4-(trifluoromethyl)phenyl benzothiazol-4-yl 19382-{[hydroxy(phenyl)acetyl[amino 1-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 19392-{[hydroxy(phenyl)acetyl]amino 1-4- 2-amino-1,3-benzothiazol- NH(trifluoromethyl)phenyl 4-yl 1940 2-amino-4-(trifluoromethyl)phenylquinolin-7-yl NH 1941 2-amino-4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl NH 1942 2-amino-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 19432-bromo-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1944 2-chloro-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 19452-hydroxy-4-(trifluoromethyl)phenyl quinolin-7-yl NH 19462-hydroxy-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- NH 4-yl1947 2-hydroxy-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1948 2-iodo-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 1949 2-naphthyl quinolin-7-ylNH 1950 2-piperidin-1-yl-6-(trifluoromethyl)pyridin- quinolin-7-yl NH3-yl 1951 3-(trifluoromethoxy)phenyl quinolin-7-yl NH 19523-(trifluoromethoxy)phenyl 2-aminoquinolin-8-yl NH 19533,4-difluorophenylquinolin-7-yl NH 1954 3-chloro-4-fluorophenylquinolin-7-yl NH 1955 3-fluoro-4-methylphenyl quinolin-7-yl NH 19564-(1-phenylethyl)piperazin-1-yl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1957 4-(2-fluorophenyl)piperazin-1-yl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 1958 4-(dimethylamino)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 19594-(trifluoromethoxy)phenyl quinolin-7-yl NH 19604-(trifluoromethoxy)phenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl1961 4-(trifluoromethyl)-2- 2-(acetylamino)-1,3- NH[(trifluoromethyl)sulfonyl]oxy}phenyl benzothiazol-4-yl 19624-(trifluoromethyl)-2-{[4- 2-(acetylamino)-1,3- NH(trifluoromethyl)benzoyl]amino}phenyl benzothiazol-4-yl 19634-(trifluoromethyl)cyclohex-1-en-1-yl 2-amino-1,3-benzothiazol-4-yl NH1964 4-(trifluoromethyl)cyclohex-1-en-1-yl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 1965 4-(trifluoromethyl)phenyl 1,3-benzothiazol-4-ylNH 1966 4-(trifluoromethyl)phenyl 1,3-benzothiazol-5-yl NH 19674-(trifluoromethyl)phenyl 1H-benzimidazol-5-yl NH 19684-(trifluoromethyl)phenyl 1H-indazol-5-yl NH 19694-(trifluoromethyl)phenyl 1H-indol-4-yl NH 19704-(trifluoromethyl)phenyl 1H-indol-5-yl NH 19714-(trifluoromethyl)phenyl 1-methyl-2-oxo-1,2- NH dihydroquinoxalin-5-yl1972 4-(trifluoromethyl)phenyl 1-naphthyl NH 19734-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 19744-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NH benzoxazol-4-yl 19754-(trifluoromethyl)phenyl 2-(acetylamino)quinolin-8- NH 19764-(trifluoromethyl)phenyl 2-(aminocarbonyl)-1,3- NH benzothiazol-4-yl1977 4-(trifluoromethyl)phenyl 2-(hydroxymethyl)-2,3- NHdihydro-1,4-benzodioxin-6-yl 1978 4-(trifluoromethyl)phenyl2-(lactoylamino)-1,3- NH benzothiazol-4-yl 19794-(trifluoromethyl)phenyl 2-(methylamino)quinolin-8- NH 19804-(trifluoromethyl)phenyl 2-(pyridin-2-ylamino)-1,3- NHbenzothiazol-4-yl 1981 4-(trifluoromethyl)phenyl 2,3-dihydro-1,4- NHbenzodioxin-6-yl 1982 4-(trifluoromethyl)phenyl2,3-dimethyl-1H-indol-6-yl NH 1983 4-(trifluoromethyl)phenyl2,6-diamino-1,3- NH benzothiazol-4-yl 1984 4-(trifluoromethyl)phenyl2-amino-1,3-benzothiazol- NH 4-yl 1985 4-(trifluoromethyl)phenyl2-aminoimidazo[1,2- NH a]pyridin-8-yl 1986 4-(trifluoromethyl)phenyl2-aminoquinazolin-8-yl NH 1987 4-(trifluoromethyl)phenyl2-aminoquinolin-7-yl NH 1988 4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl NB 1989 4-(trifluoromethyl)phenyl2-aminoquinoxalin-5-yl NB 1990 4-(trifluoromethyl)phenyl2-chloro-1,3-benzothiazol- NH 4-yl 1991 4-(trifluoromethyl)phenyl2-chloroquinolin-8-yl NH 1992 4-(trifluoromethyl)phenyl 2-hydroxy-1,3-NH benzothiazol-4-yl 1993 4-(trifluoromethyl)phenyl 2-hydroxy4- NHmethylquinolin-7-yl 1994 4-(trifluoromethyl)phenyl2-hydroxyquinolin-7-yl NH 1995 4-(trifluoromethyl)phenyl2-hydroxyquinoxalin-5-yl NH 1996 4-(trifluoromethyl)phenyl2-methyl-1,3-benzothiazol- NH 5-yl 1997 4-(trifluoromethyl)phenyl2-naphthyl NH 1998 4-(trifluoromethyl)phenyl 2-oxo-1,2,3,4- NHtetrahydroquinolin-7-yl 1999 4-(trifluoromethyl)phenyl 2-oxo-1,2,3,4- NHtetrahydroquinoxalin-5-yl 2000 4-(trifluoromethyl)phenyl2-pyridin-4-yl-1,3- NH benzothiazol-4-yl 2001 4-(trifluoromethyl)phenyl3-(1-hydroxy-1- NH methylethyl)quinolin-7-yl 20024-(trifluoromethyl)phenyl 3-(1-hydroxyethyl)quinolin- NH 7-yl 20034-(trifluoromethyl)phenyl 3-(hydroxymethyl)-1,2,3,4- NHtetrahydroquinolin-7-yl 2004 4-(trifluoromethyl)phenyl3-(hydroxymethyl)-2-oxo- NH 1,2,3,4-tetrahydroquinolin- 7-yl 20054-(trifluoromethyl)phenyl 3-(hydroxymethyl)quinolin- NH 7-yl 20064-(trifluoromethyl)phenyl 3- NH (methoxycarbonyl)quinolin 7-yl 20074-(trifluoromethyl)phenyl 3,4-dimethyiphenyl NH 20084-(trifluoromethyl)phenyl 3-amino-2-oxo-1,2- NH dihydroquinoxalin-5-yl2009 4-(trifluoromethyl)phenyl 3-aminoquinoxalin-5-yl NH 20104-(trifluoromethyl)phenyl 3-chloro-2-methylphenyl NH 20114-(trifluoromethyl)phenyl 3-oxo-1,2,3,4- NH tetrahydroisoquinolin-8-yl2012 4-(trifluoromethyl)phenyl 4-(methylamino)quinazolin- NH 8-yl 20134-(trifluoromethyl)phenyl 4-aminoquinazolin-8-yl NH 20144-(trifluoromethyl)phenyl 4-methylquinolin-8-yl NH 20154-(trifluoromethyl)phenyl isoquinolin-5-yl NH 20164-(trifluoromethyl)phenyl isoquinolin-8-yl NH 20174-(trifluoromethyl)phenyl quinolin-5-yl NH 20184-(trifluoromethyl)phenyl quinolin-7-yl NH 20194-(trifluoromethyl)phenyl quinolin-8-yl NH 20204-(trifluoromethyl)piperidin-1-yl 2-amino-1,3-benzothiazol-4-yl NH 20214-acetyiphenyl 2-(acetylamino)-1,3- NH benzothiazol4-yl 20224-acetyiphenyl 2-amino-1,3-benzothiazol-4-yl NH 20234-benzylpiperazin-1-yl 2-(acetylamino)-1,3- NH benzothiazol4-yl 20244-bromophenyl quinolin-7-yl NH 2025 4-bromophenyl2-amino-1,3-benzothiazol-yl NH 2026 4-bromophenyl 2-(acetylamino)-1,3-NH benzothiazol-4-yl 2027 4-chlorophenyl quinolin-7-yl NH 20284′-fluoro-5-(trifluoromethyl)-1,1′-biphenyl-2- quinolin-7-yl NH yl 20294-fluorophenyl quinolin-7-yl NH 2030 4-methylphenyl2-amino-1,3-benzothiazol- NH 4-yl 2031 4-methyiphenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 2032 4-phenylpiperazin-1-yl2-(acetylamino)-1,3- NH benzothiazol-4-yl 20334-tert-butylcyclohex-1-en-1-yl 2-(acetylamino)-1,3- NH benzothiazol-4-yl2034 4-tert-butylcyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- NH 4-yl2035 4-tert-butylphenyl2,3-dihydro-1,4- NH benzodioxin-6-yl 20364-tert-butylphenyl 1H-1,2,3-benzotriazol-6-yl NH 2037 4-tert-butylphenyl3-methoxyphenyl NH 2038 4-tert-butylphenyl quinolin-7-yl NH 20394-tert-butylphenyl 1,3-benzothiazol-6-yl NH 2040 4-tert-butylphenylquinolin-7-yl NH 2041 4-tert-butylphenyl 2-methyl-1,3-benzothiazol- NH5-yl 2042 4-tert-butylphenyl 2-amino-1,3-benzothiazol- NH 4-yl 20434-tert-butylphenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 2044{4-[1-(2-fluorophenyl)ethyl]piperazin-1-yl} 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2045 {4-[ethyl(methyl)amino]phenyl}2-(acetylamino)-1,3- O benzothiazol-4-yl 2046 1-benzofuran-5-ylquinolin-7-yl O 2047 2-({[1-(tert-butoxycarbonyl)piperidin-3-2-(acetylamino)-1,3- O yl]carbonyl}amino)-4- benzothiazol-4-yl(trifluoromethyl)phenyl 2048 2-({[1-(tert-butoxycarbonyl)piperidin-4-2-(acetylainino)-1,3- O yl]methyl}amino)-4-(trifluoromethyl)phenylbenzothiazol-4-yl 2049 2-(2-pyrrolidin-1-ylethoxy)-4-2-(acetylamino)-1,3- O (trifluoromethyl)phenyl benzothiazol-4-yl 20502-(benzylamino)-4-(trifluoromethyl)phenyl quinolin-7-yl O 20512-(benzyloxy)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2052 2-(isonicotinoylamino)-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20532-(lactoylamino)-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- O4-yl 2054 2-(methoxycarbonyl)-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 2055 2-(methoxymethoxy)-4-2-amino-1,3-benzothiazol- O (trifluoromethyl)phenyl 4-yl 20562-(methylamino)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2057 2-(pentylamino)4-(trifluoromethyl)phenylquinolin-7-yl O 2058 2,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl2-(acetylamino)-1,3- O benzothiazol-4-yl 20592,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl 2-amino-1,3-benzothiazol- O4-yl 2060 2-[(2,2-dimethylpropanoyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20612-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20622-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-amino-1,3-benzothiazol- O(trifluoromethyl)phenyl 4-yl 20632-[(3-piperidin-1-ylpropanoyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20642-[(4-tert-butylbenzyl)amino]-4- quinolin-7-yl O (trifluoromethyl)phenyl2065 2-[(cyclohexylacetyl)amino]-4- 2-(acetylamino)-1,3 - O(trifluoromethyl)phenyl benzothiazol-4-yl 20662-[(cyclohexylcarbonyl)aminol-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20672-[(cyclohexylmethyl)amino]-4- 1,3-benzothiazol-6-yl O(trifluoromethyl)phenyl 2068 2-[(cyclohexylmethyl)amino]-4-quinolin-7-yl O (trifluoromethyl)phenyl 20692-[(cyclohexylmethyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20702-[(cyclohexylmethyl)amino]-6- quinolin-7-yl O(trifluoromethyl)pyridin-3-yl 2071 2-[(cyclopentylacetyl)amino]-2-(acetylamino)-1,3- O (trifluoromethyl)phenyl benzothiazol-4-yl 20722-[(cyclopropylcarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20732-[(N,N-dimethylglycyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20742-[(piperidin-3-ylmethyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20752-[(pyridin-3-ylcarbonyl)amino]- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20762-[(pyridin-4-ylmethyl)amino]-4- quinolin-7-yl O (trifluoromethyl)phenyl2077 2-[(tert-butoxycarbonyl)amino]-4- quinolin-7-yl O(trifluoromethyl)phenyl 2078 2-[(tert-butoxycarbonyl)amino]-4-2-aminoquinolin-8-yl O (trifluoromethyl)phenyl 20792-[(tert-butoxycarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20802-[2-(dimethylamino)ethoxy]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20812-{[(1-acetylpiperidin-4-yl)carbonyl]amino}- 2-(acetylamino)-1,3- O4-(trifluoromethyl)phenyl benzothiazol-4-yl 20822-{[(1-methyl-1H-imidazol-5- 2-(acetylamino)-1,3- Oyl)carbonyl]amino}-4- benzothiazol-4-yl (trifluoromethyl)phenyl 20832-{[(1-methylpiperidin-4- 2-(acetylamino)-1,3- O yl)carbonyl]ainino 1-4-benzothiazol-4-yl (trifluoromethyl)phenyl 20842-{[(1-propylpiperidin-4-yl)methyl]amino}- 2-(acetylamino)-1,3- O4-(trifluoromethyl)phenyl benzothiazol-4-yl 2085 2-{[(4-{[tert-2-(acetylamino)-1,3- O butyl(dimethyl)silyl]oxy}cyclohexyl)carbonybenzothiazol-4-yl l]amino}-4-(trifluoromethyl)phenyl 20862-{[(4-hydroxycyclohexyl)carbonyl]amino}- 2-(acetylamino)-1,3- O4-(trifluoromethyl)phenyl benzothiazol-4-yl 20872-{[hydroxy(phenyl)acetyl]amino}-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 20882-{[hydroxy(phenyl)acetyl]amino}4- 2-amino-1,3-benzothiazol- O(trifluoromethyl)phenyl 4-yl 2089 2-amino-4-(trifluoromethyl)phenylquinolin-7-yl O 2090 2-amino-4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl O 2091 2-amino-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 20922-bromo-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2093 2-chloro-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- O benzothiazol4-yl 20942-hydroxy-4-(trifluoromethyl)phenyl quinolin-7-yl O 20952-hydroxy-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- O 4-yl2096 2-hydroxy-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol4-yl 2097 2-iodo-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- O benzothiazol4-yl 2098 2-naphthyl quinolin-7-yl O2099 2-piperidin-1-yl-6-(trifluoromethyl)pyridin- quinolin-7-yl O 3-yl2100 3-(trifluoromethoxy)phenyl quinolin-7-yl O 21013-(trifluoromethoxy)phenyl 2-aminoquinolin-8-yl O 21023,4-difluorophenyl quinolin-7-yl O 2103 3-chloro-4-fluorophenylquinolin-7-yl O 2104 3-fluoro4-methylphenyl quinolin-7-yl O 21054-(1-phenylethyl)piperazin-1-yl 2-(acetylamino)-1,3- O benzothiazol-4-yl2106 4-(2-fluorophenyl)piperazin-1-yl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2107 4-(dimethylamino)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2108 4-(trifluoromethoxy)phenyl quinolin-7-yl O 21094-(trifluoromethoxy)phenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 21104-(trifluoromethyl)-2- 2-(acetylamino)-1,3- O{[(trifluoromethyl)sulfonyl]oxy}phenyl benzothiazol-4-yl 21114-(trifluoromethyl)-2-{[4- 2-(acetylamino)-1,3- O(trifluoromethyl)benzoyl]amino}phenyl benzothiazol-4-yl 21124-(trifluoromethyl)cyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- O 4-yl2113 4-(trifluoromethyl)cyclohex-1-en-1-yl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2114 4-(trifluoromethyl)phenyl 1,3-benzothiazol-4-yl O2115 4-(trifluoromethyl)phenyl 1,3-benzothiazol-5-yl O 21164-(trifluoromethyl)phenyl 1H-benzimidazol-5-yl O 21174-(trifluoromethyl)phenyl 1H-indazol-5-yl O 21184-(trifluoromethyl)phenyl 1H-indol-4-yl O 2119 4-(trifluoromethyl)phenyl1H-indol-5-yl O 2120 4-(trifluoromethyl)phenyl 1-methyl-2-oxo-1,2- Odihydroquinoxalin-5-yl 2121 4-(trifluoromethyl)phenyl 1-naphthyl O 21224-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 21234-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- O benzoxazol-4-yl 21244-(trifluoromethyl)phenyl 2-(acetylamino)quinolin-8- O yl 21254-(trifluoromethyl)phenyl 2-(aminocarbonyl)-1,3 - O benzothiazol4-yl2126 4-(trifluoromethyl)phenyl 2-(hydroxymethyl)-2,3- Odihydro-1,4-benzodioxin-6- 2127 4-(trifluoromethyl)phenyl2-(lactoylainino)-1,3- O benzothiazol4-yl 2128 4-(trifluoromethyl)phenyl2-(methylamino)quinolin-8- O yl 2129 4-(trifluoromethyl)phenyl2-(pyridin-2-ylamino)-1,3- O benzothiazol-4-yl 21304-(trifluoromethyl)phenyl 2,3-dihydro-1,4- O benzodioxin-6-yl 21314-(trifluoromethyl)phenyl 2,3-dimethyl-1H-indol-6-yl O 21324-(trifluoromethyl)phenyl 2,6-diamino-1,3- O benzothiazol4-yl 21334-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- O 4-yl 21344-(trifluoromethyl)phenyl 2-aminoimidazo[1,2- O a]pyridin-8-yl 21354-(trifluoromethyl)phenyl 2-aminoquinazolin-8-yl O 21364-(trifluoromethyl)phenyl 2-aminoquinolin-7-yl O 21374-(trifluoromethyl)phenyl 2-aminoquinolin-8-yl O 21384-(trifluoromethyl)phenyl 2-aminoquinoxalin-5-yl O 21394-(trifluoromethyl)phenyl 2-chloro-1,3-benzothiazol- O 4-yl 21404-(trifluoromethyl)phenyl 2-chloroquinolin-8-yl O 21414-(trifluoromethyl)phenyl 2-hydroxy-1,3- O benzothiazol-4-yl 21424-(trifluoromethyl)phenyl 2-hydroxy-4- O methylquinolin-7-yl 21434-(trifluoromethyl)phenyl 2-hydroxyquinolin-7-yl O 21444-(trifluoromethyl)phenyl 2-hydroxyquinoxalin-5-yl O 21454-(trifluoromethyl)phenyl 2-methyl-1,3-benzothiazol- O 5-yl 21464-(trifluoromethyl)phenyl 2-naphthyl O 2147 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- O tetrahydroquinolin-7-yl 2148 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- O tetrahydroquinoxalin-5-yl 21494-(trifluoromethyl)phenyl 2-pyridin-4-yl-1,3- O benzothiazol-4-yl 21504-(trifluoromethyl)phenyl 3-(1-hydroxy-1- O methylethyl)quinolin-7-yl2151 4-(trifluoromethyl)phenyl 3-(1-hydroxyethyl)quinolin- O 7-yl 21524-(trifluoromethyl)phenyl 3-(hydroxymethyl)-1,2,3,4- Otetrahydroquinolin-7-yl 2153 4-(trifluoromethyl)phenyl3-(hydroxymethyl)-2-oxo- O 1,2,3,4-tetrahydroquinolin- 7-yl 21544-(trifluoromethyl)phenyl 3-(hydroxymethyl)quinolin- O 7-yl 21554-(trifluoromethyl)phenyl 3- O (methoxycarbonyl)quinolin 7-yl 21564-(trifluoromethyl)phenyl 3,4-dimethyiphenyl O 21574-(trifluoromethyl)phenyl 3-amino-2-oxo-1,2- O dihydroquinoxalin-5-yl2158 4-(trifluoromethyl)phenyl 3-aminoquinoxalin-5-yl O 21594-(trifluoromethyl)phenyl 3-chloro-2-methylphenyl O 21604-(trifluoromethyl)phenyl 3-oxo-1,2,3,4- O tetrahydroisoquinolin-8-yl2161 4-(trifluoromethyl)phenyl 4-(methylamino)quinazolin- O 8-yl 21624-(trifluoromethyl)phenyl 4-aminoquinazolin-8-yl O 21634-(trifluoromethyl)phenyl 4-methylquinolin-8-yl O 21644-(trifluoromethyl)phenyl isoquinolin-5-yl O 21654-(trifluoromethyl)phenyl isoquinolin-8-yl O 21664-(trifluoromethyl)phenyl quinolin-5-yl O 2167 4-(trifluoromethyl)phenylquinolin-7-yl O 2168 4-(trifluoromethyl)phenyl quinolin-8-yl O 21694-(trifluoromethyl)piperidin-1-yl 2-amino-1,3-benzothiazol- O 4-yl 21704-acetylphenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 21714-acetylphenyl 2-amino-1,3-benzothiazol- O 4-yl 21724-benzylpiperazin-1-yl 2-(acetylamino)-1,3- O benzothiazol-4-yl 21734-bromophenyl quinolin-7-yl O 2174 4-bromophenyl2-amino-1,3-benzothiazol- O 4-yl 2175 4-bromophenyl 2-(acetylamino)-1,3-O benzothiazol-4-yl 2176 4-chlorophenyl quinolin-7-yl O 21774′-fluoro-5-(trifluoromethyl)-1,1′-biphenyl- 2-quinolin-7-yl O yl 21784-fluorophenyl quinolin-7-yl O 2179 4-methylphenyl2-amino-1,3-benzothiazol- O 4-yl 2180 4-methylphenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 2181 4-phenylpiperazin-1-yl2-(acetylamino)-1,3- O benzothiazol-4-yl 21824-tert-butylcyclohex-1-en-1-yl 2-(acetylamino)-1,3- O benzothiazol-4-yl2183 4-tert-butylcyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- O 4-yl2184 4-tert-butylphenyl 2,3-dihydro-1,4- O benzodioxin-6-yl 21854-tert-butylphenyl 1H-1,2,3-benzotriazol-6-yl O 2186 4-tert-butylphenyl3-methoxyphenyl O 2187 4-tert-butylphenyl quinolin-7-yl O 21884-tert-butylphenyl 1,3-benzothiazol-6-yl O 2189 4-tert-butylphenylquinolin-7-yl O 2190 4-tert-butylphenyl 2-methyl-1,3-benzothiazol- O5-yl 2191 4-tert-butylphenyl 2-amino-1,3-benzothiazol- O 4-yl 21924-tert-butylphenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 2193{4-[1-(2-fluorophenyl)ethyl]piperazin-1-yl} 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2194 {4-[ethyl(methyl)amino]phenyl}2-(acetylamino)-1,3- S benzothiazol-4-yl 2195 1-benzofuran-5-ylquinolin-7-yl S 2196 2-({[1-(tert-butoxycarbonyl)piperidin-3-2-(acetylamino)-1,3- S yl]carbonyl}amino)-4- benzothiazol-4-yl(trifluoromethyl)phenyl 2197 2-({[1-(tert-butoxycarbonyl)piperidin-4-2-(acetylamino)-1,3- S yl]methyl}amino)-4-(trifluoromethyl)phenylbenzothiazol-4-yl 2198 2-(2-pyrrolidin-1-ylethoxy)-4-2-(acetylamino)-1,3- S (trifluoromethyl)phenyl benzothiazol-4-yl 21992-(benzylamino)-4-(trifluoromethyl)phenyl quinolin-7-yl S 22002-(benzyloxy)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1 ,3- Sbenzothiazol4-yl 2201 2-(isonicotinoylamino)-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22022-(lactoylamino)-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- S4-yl 2203 2-(methoxycarbonyl)-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 2204 2-(methoxymethoxy)-4-2-amino-1,3-benzothiazol- S (trifluoromethyl)phenyl 4-yl 22052-(methylamino)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2206 2-(pentylamino)-4-(trifluoromethyl)phenylquinolin-7-yl S 2207 2,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl2-(acetylamino)-1,3- S benzothiazol-4-yl 22082,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl 2-amino-1,3-benzothiazol- S4-yl 2209 2-[(2,2-dimethylpropanoyl)amino]-4- 2-(acetylaxnino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22102-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22112-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-amino-1,3-benzothiazol- S(trifluoromethyl)phenyl 4-yl 22122-11(3-piperidin-1-ylpropanoyl)amino]4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22132-[(4-tert-butylbenzyl)amino]-4- quinolin-7-yl S (trifluoromethyl)phenyl2214 2-[(cyclohexylacetyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22152-[(cyclohexylcarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22162-[(cyclohexylmethyl)amino]-4- 1 ,3-benzothiazol-6-yl S(trifluoromethyl)phenyl 2217 2-[(cyclohexylmethyl)amino]-4-quinolin-7-yl S (trifluoromethyl)phenyl 22182-[(cyclohexylmethyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22192-[(cyclohexylmethyl)amino]-6- quinolin-7-yl S(trifluoromethyl)pyridin-3-yl 2220 2-[(cyclopentylacetyl)amino]-4-2-(acetylamino)-1,3- S (trifluoromethyl)phenyl benzothiazol-4-yl 22212-[(cyclopropylcarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22222-[(N,N-dimethylglycyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22232-[(piperidin-3-ylmethyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22242-[(pyridin-3-ylcarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22252-[(pyridin-4-ylmethyl)amino]-4- quinolin-7-yl S (trifluoromethyl)phenyl2226 2-[(tert-butoxycarbonyl)amino]-4- quinolin-7-yl S(trifluoromethyl)phenyl 2227 2-[(tert-butoxycarbonyl)amino]-4-2-aminoquinolin-8-yl S (trifluoromethyl)phenyl 22282-[(tert-butoxycarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22292-[2-(dimethylamino)ethoxy]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22302-{[(1-acetylpiperidin-4-yl)carbonyl]amino}- 2-(acetylamino)-1,3- S4-(trifluoromethyl)phenyl benzothiazol-4-yl 22312-{[(1-methyl-1H-imidazol-5- 2-(acetylamino)-1,3- Syl)carbonyl]amino}-4- benzothiazol-4-yl (trifluoromethyl)phenyl 22322-{[(1-methylpiperidin-4- 2-(acetylamino)-1,3- S yl)carbonyl]amino}-4-benzothiazol-4-yl (trifluoromethyl)phenyl 22332-{[(1-propylpiperidin-4-yl)methyl]amino}- 2-(acetylamino)-1,3- S4-(trifluoromethyl)phenyl benzothiazol-4-yl 2234 2-{[(4-{[tert-2-(acetylamino)-1,3- S butyl(dimethyl)silyl]oxy}cyclohexyl)carbonybenzothiazol-4-yl l]amino}-4-(trifluoromethyl)phenyl 22352-{[(4-hydroxycyclohexyl)carbonyl]amino}- 2-(acetylamino)-1,3- S4-(trifluoromethyl)phenyl benzothiazol-4-yl 2236 2-{[hydroxy(phenyl)acetyl]amino}- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 22372-{[hydroxy(phenyl)acetyl]amino}-4- 2-amino-1,3-benzothiazol- S(trifluoromethyl)phenyl 4-yl 2238 2-amino-4-(trifluoromethyl)phenylquinolin-7-yl S 2239 2-amino-4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl S 2240 2-amino-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 22412-bromo-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2242 2-chloro-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 22432-hydroxy-4-(trifluoromethyl)phenyl quinolin-7-yl S 22442-hydroxy-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- S 4-yl2245 2-hydroxy-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2246 2-iodo-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 2247 2-naphthyl quinolin-7-yl S2248 2-piperidin-1-yl-6-(trifluoromethyl)pyridin- quinolin-7-yl S 3-yl2249 3-(trifluoromethoxy)phenyl quinolin-7-yl S 22503-(trifluoromethoxy)phenyl 2-aminoquinolin-8-yl S 22513,4-difluorophenyl quinolin-7-yl S 2252 3-chloro-4-fluorophenylquinolin-7-yl S 2253 3-fluoro-4-methylphenyl quinolin-7-yl S 22544-(1-phenylethyl)piperazin-1-yl 2-(acetylamino)-1,3- S benzothiazol-4-yl2255 4-(2-fluorophenyl)piperazin-1-yl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2256 4-(dimethylamino)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2257 4-(trifluoromethoxy)phenyl quinolin-7-yl S 22584-(trifluoromethoxy)phenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl 22594-(trifluoromethyl)-2- 2-(acetylamino)-1,3- S[(trifluoromethyl)sulfonyl]oxy}phenyl benzothiazol-4-yl 22604-(trifluoromethyl)-2-{[4- 2-(acetylamino)-1,3- S(trifluoromethyl)benzoyl]amino}phenyl benzothiazol-4-yl 22614-(trifluoromethyl)cyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- S 4-yl2262 4-(trifluoromethyl)cyclohex-1-en-1-yl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2263 4-(trifluoromethyl)phenyl 1,3-benzothiazol-4-yl S2264 4-(trifluoromethyl)phenyl 1,3-benzothiazol-5 -yl S 22654-(trifluoromethyl)phenyl 1H-benzirnidazol-5-yl S 22664-(trifluoromethyl)phenyl 1H-indazol-5-yl S 22674-(trifluoromethyl)phenyl 1H-indol-4-yl S 2268 4-(trifluoromethyl)phenyl1H-indol-5-yl S 2269 4-(trifluoromethyl)phenyl 1-methyl-2-oxo-1,2- Sdihydroquinoxalin-5-yl 2270 4-(trifluoromethyl)phenyl 1-naphthyl S 22714-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl 22724-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- S benzoxazol-4-yl 22734-(trifluoromethyl)phenyl 2-(acetylamino)quinolin-8- S yl 22744-(trifluoromethyl)phenyl 2-(aminocarbonyl)-1,3- S benzothiazol4-yl 22754-(trifluoromethyl)phenyl 2-(hydroxymethyl)-2,3- Sdihydro-1,4-benzodioxin-6- 2276 4-(trifluoromethyl)phenyl2-(lactoylamino)-1,3- S benzothiazol4-yl 2277 4-(trifluoromethyl)phenyl2-(methylamino)quinolin-8- S yl 2278 4-(trifluoromethyl)phenyl2-(pyridin-2-ylamino)-1,3- S benzothiazol-4-yl 22794-(trifluoromethyl)phenyl 2,3-dihydro-1,4- S benzodioxin-6-yl 22804-(trifluoromethyl)phenyl 2,3-dimethyl-1H-indol-6-yl S 22814-(trifluoromethyl)phenyl 2,6-diamino-1,3- S benzothiazol-4-yl 22824-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- S 4-yl 22834-(trifluoromethyl)phenyl 2-aminoimidazo[1,2- S a]pyridin-8-yl 22844-(trifluoromethyl)phenyl 2-aminoquinazolin-8-yl S 22854-(trifluoromethyl)phenyl 2-aminoquinolin-7-yl S 22864-(trifluoromethyl)phenyl 2-aminoquinolin-8-yl S 22874-(trifluoromethyl)phenyl 2-aminoquinoxalin-5-yl S 22884-(trifluoromethyl)phenyl 2-chloro-1,3-benzothiazol- S 4-yl 22894-(trifluoromethyl)phenyl 2-chloroquinolin-8-yl S 22904-(trifluoromethyl)phenyl 2-hydroxy-1,3- S benzothiazol-4-yl 22914-(trifluoromethyl)phenyl 2-hydroxy-4- S methylquinolin-7-yl 22924-(trifluoromethyl)phenyl 2-hydroxyquinolin-7-yl S 22934-(trifluoromethyl)phenyl 2-hydroxyquinoxalin-5-yl S 22944-(trifluoromethyl)phenyl 2-methyl-1,3-benzothiazol- S 5-yl 22954-(trifluoromethyl)phenyl 2-naphthyl S 2296 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- S tetrahydroquinolin-7-yl 2297 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- S tetrahydroquinoxalin-5-yl 22984-(trifluoromethyl)phenyl 2-pyridin-4-yl-1,3- S benzothiazol-4-yl 22994-(trifluoromethyl)phenyl 3-(1-hydroxy-1- S methylethyl)quinolin-7-yl2300 4-(trifluoromethyl)phenyl 3-(1-hydroxyethyl)quinolin- S 7-yl 23014-(trifluoromethyl)phenyl 3-(hydroxymethyl)-1,2,3,4- Stetrahydroquinolin-7-yl 2302 4-(trifluoromethyl)phenyl3-(hydroxymethyl)-2-oxo- S 1,2,3,4-tetrahydroquinolin- 7-yl 23034-(trifluoromethyl)phenyl 3-(hydroxymethyl)quinolin- S 7-yl 23044-(trifluoromethyl)phenyl 3-(methoxycarbonyl)quinolin- S 7-yl 23054-(trifluoromethyl)phenyl 3,4-dimethyiphenyl S 23064-(trifluoromethyl)phenyl 3-amino-2-oxo-1,2- S dihydroquinoxalin-5-yl2307 4-(trifluoromethyl)phenyl 3-aminoquinoxalin-5-yl S 23084-(trifluoromethyl)phenyl 3-chloro-2-methylphenyl S 23094-(trifluoromethyl)phenyl 3-oxo-1,2,3,4- S tetrahydroisoquinolin-8-yl2310 4-(trifluoromethyl)phenyl 4-(methylamino)quinazolin- S 8-yl 23114-(trifluoromethyl)phenyl 4-aminoquinazolin-8-yl S 23124-(trifluoromethyl)phenyl 4-methylquinolin-8-yl S 23134-(trifluoromethyl)phenyl isoquinolin-5-yl S 23144-(trifluoromethyl)phenyl isoquinolin-8-yl S 23154-(trifluoromethyl)phenyl quinolin-5-yl S 2316 4-(trifluoromethyl)phenylquinolin-7-yl S 2317 4-(trifluoromethyl)phenyl quinolin-8-yl S 23184-(trifluoromethyl)piperidin-1-yl 2-amino-1,3-benzothiazol- S 4-yl 23194-acetylphenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl 23204-acetylphenyl 2-amino-1,3-benzothiazol- S 4-yl 23214-benzylpiperazin-1-yl 2-(acetylamino)-1,3- S benzothiazol-4-yl 23224-bromophenyl quinolin-7-yl S 2323 4-bromophenyl2-amino-1,3-benzothiazol- S 4-yl 2324 4-bromophenyl 2-(acetylamino)-1,3-S benzothiazol-4-yl 2325 4-chlorophenyl quinolin-7-yl S 23264-fluoro-5-(trifluoromethyl)-1,1′-biphenyl-2- quinolin-7-yl S yl 23274-fluorophenyl quinolin-7-yl S 2328 4-methyiphenyl2-amino-1,3-benzothiazol- S 4-yl 2329 4-methylphenyl2-(acetylamino)-1,3-S benzothiazol-4-yl 2330 4-phenylpiperazin-1-yl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2331 4-tert-butylcyclohex-1-en-1-yl2-(acetylamino)-1,3- S benzothiazol-4-yl 23324-tert-butylcyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- S 4-yl 23334-tert-butyiphenyl2,3-dihydro-1,4- S benzodioxin-6-yl 23344-tert-butylphenyl 1H-1,2,3-benzotriazol-6-yl S 2335 4-tert-butylphenyl3-methoxyphenyl S 2336 4-tert-butylphenyl quinolin-7-yl S 23374-tert-butylphenyl 1,3-benzothiazol-6-yl S 2338 4-tert-butylphenylquinolin-7-yl S 2339 4-tert-butylphenyl 2-methyl-1,3-benzothiazol- S5-yl 2340 4-tert-butyiphenyl 2-amino-1,3-benzothiazol- S 4-yl 23414-tert-butyiphenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl

TABLE 4

Ex # R¹ R⁴ J 2342 {4-[-(2-fluorophenyl)ethyl]piperazin-1-yl}2-(acetylamino)-1,3- NH benzothiazol-4-yl 2343{4-[ethyl(methyl)amino]phenyl} 2-(acetylamino)-1,3- NH benzothiazol-4-yl2344 1-benzofuran-5-yl quinolin-7-yl NH 23452-({[1-(tert-butoxycarbonyl)piperidin-3- 2-(acetylamino)-1,3- NHyl]carbonyl}amino)-4- benzothiazol-4-yl (trifluoromethyl)phenyl 23462-({[1-(tert-butoxycarbonyl)piperidin-4- 2-(acetylamino)-1,3- NHyl]methyl}amino)-4-(trifluoromethyl)phenyl benzothiazol-4-yl 23472-(2-pyrrolidin-1-ylethoxy)-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23482-(benzylamino)-4-(trifluoromethyl)phenyl quinolin-7-yl NH 23492-(benzyloxy)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 2350 2-(isonicotinoylamino)-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23512-(lactoylamino)-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- NH4-yl 2352 2-(methoxycarbonyl)-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 2353 2-(methoxymethoxy)-4-2-amino-1,3-benzothiazol- NH (trifluoromethyl)phenyl 4-yl 23542-(methylamino)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 2355 2-(pentylamino)-4-(trifluoromethyl)phenylquinolin-7-yl NH 2356 2,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl2-(acetylamino)-1,3- NH benzothiazol4-yl 23572,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl 2-amino-1,3-benzothiazol- NH4-yl 2358 2-[(2,2-dimethylpropanoyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23592-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23602-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-amino-1,3-benzothiazol- NH(trifluoromethyl)phenyl 4-yl 2361 2-[(3-piperidin-1-ylpropanoyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23622-[(4-tert-butylbenzyl)amino]-4- quinolin-7-yl NH(trifluoromethyl)phenyl 2363 2-[(cyclohexylacetyl)amino]-4-2-(acetylamino)-1,3- NH (trifluoromethyl)phenyl benzothiazol-4-yl 23642-[(cyclohexylcarbonyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23652-[(cyclohexylmethyl)amino]-4- 1,3-benzothiazol-6-yl NH(trifluoromethyl)phenyl 2366 2-[(cyclohexylmethyl)amino]-4-quinolin-7-yl NH (trifluoromethyl)phenyl 23672-[(cyclohexylmethyl)aniino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23682-[(cyclohexylmethyl)amino]-6- quinolin-7-yl NH(trifluoromethyl)pyridin-3-yl 2369 2-[(cyclopentylacetyl)amino]-4-2-(acetylamino)-1,3- NH (trifluoromethyl)phenyl benzothiazol-4-yl 23702-[(cyclopropylcarbonyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23712-[(N,N-dimethylglycyl)amino]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23722-[(piperidin-3-ylmethyl)amino]- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23732-[(pyridin-3-ylcarbonyl)amino]- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23742-[(pyridin-4-ylmethyl)amino]-4- quinolin-7-yl NH(trifluoromethyl)phenyl 2375 2-[(tert-butoxycarbonyl)amino]-4-quinolin-7-yl NH (trifluoromethyl)phenyl 23762-[(tert-butoxycarbonyl)amino]-4- 2-aminoquinolin-8-yl NH(trifluoromethyl)phenyl 2377 2-[(tert-butoxycarbonyl)amino]-4-2-(acetylainino)-1,3- NH (trifluoromethyl)phenyl benzothiazol-4-yl 23782-[2-(dimethylamino)ethoxy]-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23792-{[(1-acetylpiperidin-4-yl)carbonyl]amino}- 2-(acetylamino)-1,3- NH4-(trifluoromethyl)phenyl benzothiazol-4-yl 23802-{[(1-methyl-1H-imidazol-5- 2-(acetylamino)-1,3- NH yl)carbonyl]amino1-4- benzothiazol-4-yl (trifluoromethyl)phenyl 2381 2-{[(1-methylpiperidin-4- 2-(acetylamino)-1,3- NH yl)carbonyl]amino}-4-benzothiazol-4-yl (trifluoromethyl)phenyl 2382 2-{[(1-propylpiperidin-4-yl)methyl]amino}- 2-(acetylamino)-1,3- NH4-(trifluoromethyl)phenyl benzothiazol-4-yl 23832-{[(4-{[tert-2-(acetylamino)- 1,3-benzothiazol-4-yl NHbutyl(dimethyl)silyl]oxy}cyclohexyl)carbonyl]amino}-4-(trifluoromethyl)phenyl 23842-{[(4-hydroxycyclohexyl)carbonyl]amino}- 2-(acetylamino)-1,3- NH4-(trifluoromethyl)phenyl benzothiazol-4-yl 23852-{[hydroxy(phenyl)acetyl]amino}-4- 2-(acetylamino)-1,3- NH(trifluoromethyl)phenyl benzothiazol-4-yl 23862-{[hydroxy(phenyl)acetyl]amino}-4- 2-amino-1,3-benzothiazol- NH(trifluoromethyl)phenyl 4-yl 2387 2-amino-4-(trifluoromethyl)phenylquinolin-7-yl NH 2388 2-amino-4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl NH 2389 2-amino-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 23902-bromo-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 2391 2-chloro-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 23922-hydroxy-4-(trifluoromethyl)phenyl quinolin-7-yl NH 23932-hydroxy-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- NH 4-yl2394 2-hydroxy-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 2395 2-iodo-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 2396 2-naphthyl quinolin-7-ylNH 2397 2-piperidin-1-yl-6-(trifluoromethyl)pyridin- quinolin-7-yl NH3-yl 2398 3-(trifluoromethoxy)phenyl quinolin-7-yl NH 23993-(trifluoromethoxy)phenyl 2-aminoquinolin-8-yl NH 24003,4-difluorophenyl quinolin-7-yl NH 2401 3-chloro-4-fluorophenylquinolin-7-yl NH 2402 3-fluoro-4-methylphenyl quinolin-7-yl NH 24034-(1-phenylethyl)piperazin-1-yl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 2404 4-(2-fluorophenyl)piperazin-1-yl2-(acetylainino)-1,3- NH benzothiazol-4-yl 2405 4-(dimethylamino)phenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 24064-(trifluoromethoxy)phenyl quinolin-7-yl NH 24074-(trifluoromethoxy)phenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl2408 4-(trifluoromethyl)-2- 2-(acetylamino)-1,3- NH{[(trifluoromethyl)sulfonyl]oxy}phenyl benzothiazol-4-yl 24094-(trifluoromethyl)-2-{[4- 2-(acetylamino)-1,3- NH(trifluoromethyl)benzoyl]amino}phenyl benzothiazol-4-yl 24104-(trifluoromethyl)cyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- NH 4-yl2411 4-(trifluoromethyl)cyclohex-1-en-1-yl 2-(acetylamino)-1,3- NHbenzothiazol-4-yl 2412 4-(trifluoromethyl)phenyl 1,3-benzothiazol-4-ylNH 2413 4-(trifluoromethyl)phenyl 1,3-benzothiazol-5-yl NH 24144-(trifluoromethyl)phenyl 1H-benzimidazol-5-yl NH 24154-(trifluoromethyl)phenyl 1H-indazol-5-yl NH 24164-(trifluoromethyl)phenyl 1H-indol4-yl NH 2417 4-(trifluoromethyl)phenyl1H-indol-5-yl NH 2418 4-(trifluoromethyl)phenyl 1-methyl-2-oxo-1,2- NHdihydroquinoxalin-5-yl 2419 4-(trifluoromethyl)phenyl 1-naphthyl NH 24204-(trifluoromethyl)phenyl 2-(acetylaimno)-1,3- NH benzothiazol-4-yl 24214-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- NH benzoxazol-4-yl 24224-(trifluoromethyl)phenyl 2-(acetylamino)quinolin-8- NH yl 24234-(trifluoromethyl)phenyl 2-(aminocarbonyl)-1,3- NH benzothiazol-4-yl2424 4-(trifluoromethyl)phenyl 2-(hydroxymethyl)-2,3- NHdihydro-1,4-benzodioxin-6- 2425 4-(trifluoromethyl)phenyl2-(lactoylamino)-1,3- NH benzothiazol-4-yl 24264-(trifluoromethyl)phenyl 2-(methylamino)quinolin-8- NH yl 24274-(trifluoromethyl)phenyl 2-(pyridin-2-ylamino)-1,3- NHbenzothiazol-4-yl 2428 4-(trifluoromethyl)phenyl 2,3-dihydro-1,4- NHbenzodioxin-6-yl 2429 4-(trifluoromethyl)phenyl2,3-dimethyl-1H-indol-6-yl NH 2430 4-(trifluoromethyl)phenyl2,6-diainino-1,3- NH benzothiazol-4-yl 2431 4-(trifluoromethyl)phenyl2-amino-1,3-benzothiazol- NH 4-yl 2432 4-(trifluoromethyl)phenyl2-aminoimidazo[1,2- NH a]pyridin-8-yl 2433 4-(trifluoromethyl)phenyl2-aminoquinazolin-8-yl NH 2434 4-(trifluoromethyl)phenyl2-aminoquinolin-7-yl NH 2435 4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl NH 2436 4-(trifluoromethyl)phenyl2-aminoquinoxalin-5-yl NH 2437 4-(trifluoromethyl)phenyl2-chloro-1,3-benzothiazol- NH 4-yl 2438 4-(trifluoromethyl)phenyl2-chloroquinolin-8-yl NH 2439 4-(trifluoromethyl)phenyl 2-hydroxy-1,3-NH benzothiazol-4-yl 2440 4-(trifluoromethyl)phenyl 2-hydroxy-4- NHmethylquinolin-7-yl 2441 4-(trifluoromethyl)phenyl2-hydroxyquinolin-7-yl NH 2442 4-(trifluoromethyl)phenyl2-hydroxyquinoxalin-5-yl NH 2443 4-(trifluoromethyl)phenyl2-methyl-1,3-benzothiazol- NH 5-yl 2444 4-(trifluoromethyl)phenyl2-naphthyl NH 2445 4-(trifluoromethyl)phenyl 2-oxo-1,2,3,4- NHtetrahydroquinolin-7-yl 2446 4-(trifluoromethyl)phenyl 2-oxo-1,2,3,4- NHtetrahydroquinoxalin-5-yl 2447 4-(trifluoromethyl)phenyl2-pyridin-4-yl-1,3- NH benzothiazol-4-yl 2448 4-(trifluoromethyl)phenyl3-(1-hydroxy-1- NH methylethyl)quinolin-7-yl 24494-(trifluoromethyl)phenyl 3-(1-hydroxyethyl)quinolin- NH 7-yl 24504-(trifluoromethyl)phenyl 3-(hydroxymethyl)-1,2,3,4- NHtetrahydroquinolin-7-yl 2451 4-(trifluoromethyl)phenyl3-(hydroxymethyl)-2-oxo- NH 1,2,3,4-tetrahydroquinolin- 7-yl 24524-(trifluoromethyl)phenyl 3-(hydroxymethyl)quinolin- NH 7-yl 24534-(trifluoromethyl)phenyl 3-(methoxycarbonyl)quinolin NH 7-yl 24544-(trifluoromethyl)phenyl 3,4-dimethylphenyl NH 24554-(trifluoromethyl)phenyl 3-amino-2-oxo-1,2- NH dihydroquinoxalin-5-yl2456 4-(trifluoromethyl)phenyl 3-aminoquinoxalin-5-yl NH 24574-(trifluoromethyl)phenyl 3-chloro-2-methylphenyl NH 24584-(trifluoromethyl)phenyl 3-oxo-1,2,3,4- NH tetrahydroisoquinolin-8-yl2459 4-(trifluoromethyl)phenyl 4-(methylamino)quinazolin- NH 8-yl 24604-(trifluoromethyl)phenyl 4-aminoquinazolin-8-yl NH 24614-(trifluoromethyl)phenyl 4-methylquinolin-8-yl NH 24624-(trifluoromethyl)phenyl isoquinolin-5-yl NH 24634-(trifluoromethyl)phenyl isoquinolin-8-yl NH 24644-(trifluoromethyl)phenyl quinolin-5-yl NH 24654-(trifluoromethyl)phenyl quinolin-7-yl NH 24664-(trifluoromethyl)phenyl quinolin-8-yl NH 24674-(trifluoromethyl)piperidin-1-yl 2-amino-1,3-benzothiazol- NH 4-yl 24684-acetylphenyl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 24694-acetylphenyl 2-amino-1,3-benzothiazol- NH 4-yl 24704-benzylpiperazin-1-yl 2-(acetylamino)-1,3- NH benzothiazol-4-yl 24714-bromophenyl quinolin-7-yl NH 2472 4-bromophenyl2-amino-1,3-benzothiazol- NH 4-yl 2473 4-bromophenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 2474 4-chlorophenylquinolin-7-yl NH 2475 4′-fluoro-5-(trifluoromethyl)-1,1′-biphenyl-2-quinolin-7-yl NH yl 2476 4-fluorophenyl quinolin-7-yl NH 24774-methylphenyl 2-amino-1,3-benzothiazol- NH 4-yl 2478 4-methylphenyl2-(acetylamino)-1,3- NH benzothiazol-4-yl 2479 4-phenylpiperazin-1-yl2-(acetylamino)-1,3- NH benzothiazol-4-yl 24804-tert-butylcyclohex-1-en-1-yl 2-(acetylamino)-1,3- NH benzothiazol-4-yl2481 4-tert-butylcyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- NH 4-yl2482 4-tert-butylphenyl 2,3-dihydro-1,4- NH benzodioxin-6-yl 24834-tert-butylphenyl 1H-1,2,3-benzotriazol-6-yl NH 2484 4-tert-butylphenyl3-methoxyphenyl NH 2485 4-tert-butylphenyl quinolin-7-yl NH 24864-tert-butylphenyl 1,3-benzothiazol-6-yl NH 2487 4-tert-butylphenylquinolin-7-yl NH 2488 4-tert-butylphenyl 2-methyl-1,3-benzothiazol- NH5-yl 2489 4-tert-butylphenyl 2-amino-1,3-benzothiazol- NH 4-yl 24904-tert-butylphenyl2-(acetylamino)-i ,3- NH benzothiazol-4-yl 2491{4-[1-(2-fluorophenyl)ethyl]piperazin-1-yl} 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2492 {4-[ethyl(methyl)amino]phenyl}2-(acetylamino)-1,3- O benzothiazol-4-yl 2493 1-benzofuran-5-ylquinolin-7-yl O 2494 2-({[1-(tert-butoxycarbonyl)piperidin-3-2-(acetylamino)-1,3- O yl]carbonyl}amino)4- benzothiazol-4-yl(trifluoromethyl)phenyl 2495 2-({[1-(tert-butoxycarbonyl)piperidin-4-2-(acetylamino)-1,3- O yl]methyl}amino)-4-(trifluoromethyl)phenylbenzothiazol-4-yl 2496 2-(2-pyrrolidin-1-ylethoxy)-4-2-(acetylamino)-1,3- O (trifluoromethyl)phenyl benzothiazol-4-yl 24972-(benzylamino)-4-(trifluoromethyl)phenyl quinolin-7-yl O 24982-(benzyloxy)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2499 2-(isonicotinoylamino)-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 25002-(lactoylamino)-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- O4-yl 2501 2-(methoxycarbonyl)-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 2502 2-(methoxymethoxy)-4-2-amino-1,3-benzothiazol- O (trifluoromethyl)phenyl 4-yl 25032-(methylamino)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2504 2-(pentylamino)4-(trifluoromethyl)phenylquinolin-7-yl O 2505 2,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl2-(acetylamino)-1,3- O benzothiazol-4-yl 25062,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl 2-amino-1,3-benzothiazol- O4-yl 2507 2-[(2,2-dimethylpropanoyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 25082-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 25092-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-amino-1,3-benzothiazol- O(trifluoromethyl)phenyl 4-yl 2510 2-V3-piperidin-1-ylpropanoyl)amino]-4- 2-(acetylamino)-1,3- O (trifluoromethyl)phenylbenzothiazol-4-yl 2511 2-[(4-tert-butylbenzyl)amino]-4- quinolin-7-yl O(trifluoromethyl)phenyl 2512 2-[(cyclohexylacetyl)aminoj-4-2-(acetylamino)-1,3- O (trifluoromethyl)phenyl benzothiazol-4-yl 25132-[(cyclohexylcarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 25142-[(cyclohexylmethyl)amino]-4- 1,3-benzothiazol-6-yl O(trifluoromethyl)phenyl 2515 2-[(cyclohexylmethyl)amino]-4-quinolin-7-yl O (trifluoromethyl)phenyl 25162-[(cyclohexylmethyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 25172-[(cyclohexylmethyl)amino]-6- quinolin-7-yl O(trifluoromethyl)pyridin-3-yl 2518 2-[(cyclopentylacetyl)amino]-4-2-(acetylamino)-1,3- O (trifluoromethyl)phenyl benzothiazol-4-yl 25192-[(cyclopropylcarbonyl)amino]-4- 2-(acetylarnino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 25202-[(N,N-dimethylglycyl)amino]-4- 2-(acetylainino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 25212-[(piperidin-3-ylmethyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 25222-[(pyridin-3-ylcarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol4-yl 25232-[(pyridin-4-ylmethyl)amino]-4- quinolin-7-yl O (trifluoromethyl)phenyl2524 2-[(tert-butoxycarbonyl)amino]-4- quinolin-7-yl O(trifluoromethyl)phenyl 2525 2-[(tert-butoxycarbonyl)ainino]-4-2-aminoquinolin-8-yl O (trifluoromethyl)phenyl 25262-[(tert-butoxycarbonyl)amino]-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol4-yl 25272-[2-(dimethylamino)ethoxy]4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 25282-{[(1-acetylpiperidin-4-yl)carbonyl]amino}- 2-(acetylamino)-1,3- O4-(trifluoromethyl)phenyl benzothiazol-4-yl 25292-{[(1-methyl-1H-imidazol-5- 2-(acetylamino)-1,3- Oyl)carbonyl]amino}-4- benzothiazol-4-yl (trifluoromethyl)phenyl 25302-{[(1-methylpiperidin-4- 2-(acetylamino)-1,3- O yl)carbonyl]amino}-benzothiazol-4-yl (trifluoromethyl)phenyl 25312-{[(1-propylpiperidin-4-yl)methyl]amino}- 2-(acetylamino)-1,3- O4-(trifluoromethyl)phenyl benzothiazol-4-yl 2532 2-{[(4-{[tert-2-(acetylamino)-1,3- O butyl(dimethyl)silyl]oxy}cyclohexyl)carbonybenzothiazol-4-yl l]amino}4-(trifluoromethyl)phenyl 2533 2-4[(4-hydroxycyclohexyl)carbonyl]amino}- 2-(acetylamino)-1,3- O4-(trifluoromethyl)phenyl benzothiazol-4-yl 2534 2-4[hydroxy(phenyl)acetyl]amino}-4- 2-(acetylamino)-1,3- O(trifluoromethyl)phenyl benzothiazol-4-yl 2535 2-4[hydroxy(phenyl)acetyl]amino 1-4- 2-amino-1,3-benzothiazol- O(trifluoromethyl)phenyl 4-yl 2536 2-amino-4-(trifluoromethyl)phenylquinolin-7-yl O 2537 2-amino-4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl O 2538 2-amino-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 25392-bromo4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2540 2-chloro-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- O benzothiazol4-yl 25412-hydroxy4-(trifluoromethyl)phenyl quinolin-7-yl O 25422-hydroxy-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- O 4-yl2543 2-hydroxy-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2544 2-iodo-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 2545 2-naphthyl quinolin-7-yl O2546 2-piperidin-1-yl-6-(trifluoromethyl)pyridin- quinolin-7-yl O 3-yl2547 3-(trifluoromethoxy)phenyl quinolin-7-yl O 25483-(trifluoromethoxy)phenyl 2-aminoquinolin-8-yl O 25493,4-difluorophenyl quinolin-7-yl O 2550 3-chloro-4-fluorophenylquinolin-7-yl O 2551 3-fluoro-4-methylphenyl quinolin-7-yl O 25524-(1-phenylethyl)piperazin-1-yl 2-(acetylamino)-1,3- O benzothiazol-4-yl2553 4-(2-fluorophenyl)piperazin-1-yl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2554 4-(dimethylamino)phenyl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2555 4-(trifluoromethoxy)phenyl quinolin-7-yl O 25564-(trifluoromethoxy)phenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 25574-(trifluoromethyl)-2- 2-(acetylamino)-1,3- O{[(trifluoromethyl)sulfonyl]oxy}phenyl benzothiazol-4-yl 25584-(trifluoromethyl)-2-{[4- 2-(acetylamino)-1,3- O(trifluoromethyl)benzoyl]amino}phenyl benzothiazol-4-yl 25594-(trifluoromethyl)cyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- O 4-yl2560 4-(trifluoromethyl)cyclohex-1-en-1-yl 2-(acetylamino)-1,3- Obenzothiazol-4-yl 2561 4-(trifluoromethyl)phenyl 1,3-benzorhiazol-4-yl O2562 4-(trifluoromethyl)phenyl 1,3-benzothiazol-5-yl O 25634-(trifluoromethyl)phenyl 1H-benzimidazol-5-yl O 25644-(trifluoromethyl)phenyl 1H-indazol-5-yl O 25654-(trifluoromethyl)phenyl 1H-indol4-yl O 2566 4-(trifluoromethyl)phenyl1H-indol-5-yl O 2567 4-(trifluoromethyl)phenyl 1-methyl-2-oxo-1,2- Odihydroquinoxalin-5-yl 2568 4-(trifluoromethyl)phenyl 1-naphthyl O 25694-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 25704-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- O benzoxazol-4-yl 25714-(trifluoromethyl)phenyl 2-(acetylamino)quinolin-8- O 25724-(trifluoromethyl)phenyl 2-(aminocarbonyl)-1,3- O benzothiazol-4-yl2573 4-(trifluoromethyl)phenyl 2-(hydroxymethyl)-2,3- Odihydro-1,4-benzodioxin-6- yl 2574 4-(trifluoromethyl)phenyl2-(lactoylamino)-1,3- O benzothiazol-4-yl 2575 4-(trifluoromethyl)phenyl2-(methylamino)quinolin-8- O 2576 4-(trifluoromethyl)phenyl2-(pyridin-2-ylamino)-1,3- O benzothiazol-4-yl 25774-(trifluoromethyl)phenyl 2,3-dihydro-1,4- O benzodioxin-6-yl 25784-(trifluoromethyl)phenyl 2,3-dimethyl-1H-indol-6-yl O 25794-(trifluoromethyl)phenyl 2,6-diamino-1,3- O benzothiazol-4-yl 25804-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- O 4-yl 25814-(trifluoromethyl)phenyl 2-aminoimidazo[1,2- O a]pyridin-8-yl 25824-(trifluoromethyl)phenyl 2-aminoquinazolin-8-yl O 25834-(trifluoromethyl)phenyl 2-aminoquinolin-7-yl O 25844-(trifluoromethyl)phenyl 2-aminoquinolin-8-yl O 25854-(trifluoromethyl)phenyl 2-aminoquinoxalin-5-yl O 25864-(trifluoromethyl)phenyl 2-chloro-1,3-benzothiazol- O 4-yl 25874-(trifluoromethyl)phenyl 2-chloroquinolin-8-yl O 25884-(trifluoromethyl)phenyl 2-hydroxy-1,3- O benzothiazol-4-yl 25894-(trifluoromethyl)phenyl 2-hydroxy-4- O methylquinolin-7-yl 25904-(trifluoromethyl)phenyl 2-hydroxyquinolin-7-yl O 25914-(trifluoromethyl)phenyl 2-hydroxyquinoxalin-5-yl O 25924-(trifluoromethyl)phenyl 2-methyl-1,3-benzothiazol- O 5-yl 25934-(trifluoromethyl)phenyl 2-naphthyl O 2594 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- O tetrahydroquinolin-7-yl 2595 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- O tetrahydroquinoxalin-5-yl 25964-(trifluoromethyl)phenyl 2-pyridin4-yl-1,3- O benzothiazol-4-yl 25974-(trifluoromethyl)phenyl 3-(1-hydroxy-1- O methylethyl)quinolin-7-yl2598 4-(trifluoromethyl)phenyl 3-(1-hydroxyethyl)quinolin- O 7-yl 25994-(trifluoromethyl)phenyl 3-(hydroxymethyl)-1,2,3,4- Otetrahydroquinolin-7-yl 2600 4-(trifluoromethyl)phenyl3-(hydroxymethyl)-2-oxo- O 1,2,3,4-tetrahydroquinolin- 7-yl 26014-(trifluoromethyl)phenyl 3-(hydroxymethyl)quinolin- O 7-yl 26024-(trifluoromethyl)phenyl 3- O (methoxycarbonyl)quinolin 7-yl 26034-(trifluoromethyl)phenyl 3,4-dimethylphenyl O 26044-(trifluoromethyl)phenyl 3-amino-2-oxo-1,2- O dihydroquinoxalin-5-yl2605 4-(trifluoromethyl)phenyl 3-aminoquinoxalin-5-yl O 26064-(trifluoromethyl)phenyl 3-chloro-2-methylphenyl O 26074-(trifluoromethyl)phenyl 3-oxo-1,2,3,4- O tetrahydroisoquinolin-8-yl2608 4-(trifluoromethyl)phenyl 4-(methylamino)quinazolin- O 8-yl 26094-(trifluoromethyl)phenyl 4-aminoquinazolin-8-yl O 26104-(trifluoromethyl)phenyl 4-methylquinolin-8-yl O 26114-(trifluoromethyl)phenyl isoquinolin-5-yl O 26124-(trifluoromethyl)phenyl isoquinolin-8-yl O 26134-(trifluoromethyl)phenyl quinolin-5-yl O 2614 4-(trifluoromethyl)phenylquinolin-7-yl O 2615 4-(trifluoromethyl)phenyl quinolin-8-yl O 26164-(trifluoromethyl)piperidin-1-yl 2-amino-1,3-benzothiazol- O 4-yl 26174-acetylphenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 26184-acetylphenyl 2-amino-1,3-benzothiazol- O 4-yl 26194-benzylpiperazin-1-yl 2-(acetylamino)-1,3- O benzothiazol-4-yl 26204-bromophenyl quinolin-7-yl O 2621 4-bromophenyl2-amino-1,3-benzothiazol- O 4-yl 2622 4-bromophenyl 2-(acetylamino)-1,3-O benzothiazol-4-yl 2623 4-chlorophenyl quinolin-7-yl O 26244′-fluoro-5-(trifluoromethyl)-1,1′-biphenyl- 2-quinolin-7-yl O yl 26254-fluorophenyl quinolin-7-yl O 2626 4-methylphenyl2-amino-1,3-benzothiazol- O 4-yl 2627 4-methylphenyl2-(acetylamino)-1,3- O benzothiazol-4-yl 2628 4-phenylpiperazin-1-yl2-(acetylamino)-1,3- O benzothiazol-4-yl 26294-tert-butylcyclohex-1-en-1-yl 2-(acetylamino)-1,3- O benzothiazol-4-yl2630 4-tert-butylcyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- O 4-yl2631 4-tert-butylphenyl 2,3-dihydro-1,4- O benzodioxin-6-yl 26324-tert-butylphenyl 1H-1,2,3-benzotriazol-6-yl O 2633 4-tert-butylphenyl3-methoxyphenyl O 2634 4-tert-butylphenyl quinolin-7-yl O 26354-tert-butylphenyl 1,3-benzothiazol-6-yl O 2636 4-tert-butyiphenylquinolin-7-yl O 2637 4-tert-butyiphenyl 2-methyl-1,3-benzothiazol- O5-yl 2638 4-tert-butylphenyl 2-amino-1,3-benzothiazol- O 4-yl 26394-tert-butylphenyl 2-(acetylamino)-1,3- O benzothiazol-4-yl 2640{4-[1-(2-fluorophenyl)ethyl]piperazin-1-yl} 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2641 {4-[ethyl(methyl)amino]phenyl}2-(acetylamino)-1,3- S benzothiazol-4-yl 2642 1-benzofuran-5-ylquinolin-7-yl S 2643 2-({[1-(tert-butoxycarbonyl)pipendin-3-2-(acetylamino)-1,3- S yl]carbonyl}amino)-4- benzothiazol-4-yl(trifluoromethyl)phenyl 2644 2-({[1-(tert-butoxycarbonyl)piperidin-4-2-(acetylamino)-1,3- S yl]methyl}amino)-4-(trifluoromethyl)phenylbenzothiazol-4-yl 2645 2-(2-pyrrolidin-1-ylethoxy)-4-2-(acetylamino)-1,3- S (trifluoromethyl)phenyl benzothiazol-4-yl 26462-(benzylamino)-4-(trifluoromethyl)phenyl quinolin-7-yl S 26472-(benzyloxy)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2648 2-(isonicotinoylamino)-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26492-(lactoylamino)-4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- S4-yl 2650 2-(methoxycarbonyl)-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 2651 2-(methoxymethoxy)-4-2-amino-1,3-benzothiazol- S (trifluoromethyl)phenyl 4-yl 26522-(methylamino)-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2653 2-(pentylamino)-4-(trifluoromethyl)phenylquinolin-7-yl S 2654 2,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl2-(acetylamino)-1,3- S benzothiazol-4-yl 26552,2-dimethyl-2,3-dihydro-1-benzofuran-6-yl 2-amino-1,3-benzothiazol- S4-yl 2656 2-[(2,2-dimethylpropanoyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26572-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26582-[(2-hydroxy-2-methylpropanoyl)amino]-4- 2-amino-1,3-benzothiazol- S(trifluoromethyl)phenyl 4-yl 26592-[(3-piperidin-1-ylpropanoyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26602-[(4-tert-butylbenzyl)amino]-4- quinolin-7-yl S (trifluoromethyl)phenyl2661 2-[(cyclohexylacetyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26622-[(cyclohexylcarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26632-[(cyclohexylmethyl)amino]-4- 1,3-benzothiazol-6-yl S(trifluoromethyl)phenyl 2664 2-[(cyclohexylmethyl)amino]-4-quinolin-7-yl S (trifluoromethyl)phenyl 26652-[(cyclohexylmethyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26662-[(cyclohexylmethyl)amino]-6- quinolin-7-yl S(trifluoromethyl)pyridin-3-yl 2667 2-[(cyclopentylacetyl)amino]-4-2-(acetylamino)-1,3- S (trifluoromethyl)phenyl benzothiazol-4-yl 26682-[(cyclopropylcarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26692-[(N,N-dimethylglycyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26702-[(piperidin-3-ylmethyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26712-[(pyridin-3-ylcarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26722-[(pyridin-4-ylmethyl)amino]-4- quinolin-7-yl S (trifluoromethyl)phenyl2673 2-[(tert-butoxycarbonyl)amino]-4- quinolin-7-yl S(trifluoromethyl)phenyl 2674 2-[(tert-butoxycarbonyl)amino]-4-2-aminoquinolin-8-yl S (trifluoromethyl)phenyl 26752-[(tert-butoxycarbonyl)amino]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26762-[2-(dimethylamino)ethoxy]-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 26772-{[(1-acetylpiperidin-4-yl)carbonyl]amino}- 2-(acetylamino)-1,3- S4-(trifluoromethyl)phenyl benzothiazol-4-yl 2678 2-4[(1-methyl-1H-imidazol-5- 2-(acetylamino)-1,3- 5 yl)carbonyl]amino}-4-benzothiazol-4-yl (trifluoromethyl)phenyl 2679 2-4[(1-methylpiperidin-4- 2-(acetylamino)-1,3- S yl)carbonyl]amino}-4-benzothiazol-4-yl (trifluoromethyl)phenyl 26802-{[(1-propylpiperidin-4-yl)methyl]amino}- 2-(acetylamino)-1,3- S4-(trifluoromethyl)phenyl benzothiazol-4-yl 2681 2-{[(4-{[tert-2-(acetylamino)-1,3- S butyl(dimethyl)silyl]oxy}cyclohexyl)carbonybenzothiazol-4-yl l]amino}-4-(trifluoromethyl)phenyl 26822-{[(4-hydroxycyclohexyl)carbonyl]amino}- 2-(acetylamino)-1,3- S4-(trifluoromethyl)phenyl benzothiazol-4-yl 26832-{[hydroxy(phenyl)acetyl]amino}-4- 2-(acetylamino)-1,3- S(trifluoromethyl)phenyl benzothiazol-4-yl 2684 2-4[hydroxy(phenyl)acetyl]amino}-4- 2-amino-1,3-benzothiazol- S(trifluoromethyl)phenyl 4-yl 2685 2-amino-4-(trifluoromethyl)phenylquinolin-7-yl S 2686 2-amino-4-(trifluoromethyl)phenyl2-aminoquinolin-8-yl S 2687 2-amino-4-(trifluoromerhyl)phenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 26882-bromo-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2689 2-chloro-4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 26902-hydroxy-4-(trifluoromethyl)phenyl quinolin-7-yl S 26912-hydroxy4-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- S 4-yl 26922-hydroxy-4-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2693 2-iodo4-(trifluoromethyl)phenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 2694 2-naphthyl quinolin-7-yl S2695 2-piperidin-1-yl-6-(trifluoromethyl)pyridin- quinolin-7-yl S 3-yl2696 3-(trifluoromethoxy)phenyl quinolin-7-yl S 26973-(trifluoromethoxy)phenyl 2-aminoquinolin-8-yl S 26983,4-difluorophenyl quinolin-7-yl S 2699 3-chloro-4-fluorophenylquinolin-7-yl S 2700 3-fluoro4-methylphenyl quinolin-7-yl S 27014-(1-phenylethyl)piperazin-1-yl 2-(acetylamino)-1,3- S benzothiazol-4-yl2702 4-(2-fluorophenyl)piperazin-1-yl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2703 4-(dimethylamino)phenyl 2-(acetylamino)-1,3- Sbenzothiazol-4-yl 2704 4-(trifluoromethoxy)phenyl quinolin-7-yl S 27054-(trifluoromethoxy)phenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl 27064-(trifluoromethyl)-2- 2-(acetylamino)-1,3- S[(trifluoromethyl)sulfonyl]oxy}phenyl benzothiazol-4-yl 27074-(trifluoromethyl)-2-{[4- 2-(acetylamino)-1,3- S(trifluoromethyl)benzoyl]amino}phenyl benzothiazol-4-yl 27084-(trifluoromethyl)cyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- S 4-yl2709 4-(trifluoromethyl)cyclohex-1-en-1-yl 2-(acetylainino)-1,3- Sbenzothiazol-4-yl 2710 4-(trifluoromethyl)phenyl 1,3-benzothiazol4-yl S2711 4-(trifluoromethyl)phenyl 1,3-benzothiazol-5-yl S 27124-(trifluoromethyl)phenyl 1H-benzimidazol-5-yl S 27134-(trifluoromethyl)phenyl 1H-indazol-5-yl S 27144-(trifluoromethyl)phenyl 1H-indol-4-yl S 2715 4-(trifluoromethyl)phenyl1H-indol-5-yl S 2716 4-(trifluoromethyl)phenyl 1-methyl-2-oxo-1,2- Sdihydroquinoxalin-5-yl 2717 4-(trifluoromethyl)phenyl 1-naphthyl S 27184-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl 27194-(trifluoromethyl)phenyl 2-(acetylamino)-1,3- S benzoxazol-4-yl 27204-(trifluoromethyl)phenyl 2-(acetylamino)quinolin-8- S yl 27214-(trifluoromethyl)phenyl 2-(aminocarbonyl)-1,3- S benzothiazol4-yl 27224-(trifluoromethyl)phenyl 2-(hydroxymethyl)-2,3- Sdihydro-1,4-benzodioxin-6- yl 2723 4-(trifluoromethyl)phenyl2-(lactoylamino)-1,3- S benzothiazol-4-yl 2724 4-(trifluoromethyl)phenyl2-(methylamino)quinolin-8- S 2725 4-(trifluoromethyl)phenyl2-(pyridin-2-ylamino)-1,3- S benzothiazol-4-yl 27264-(trifluoromethyl)phenyl 2,3-dihydro-1,4- S benzodioxin-6-yl 27274-(trifluoromethyl)phenyl 2,3-dimethyl-1H-indol-6-yl S 27284-(trifluoromethyl)phenyl 2,6-diamino-1,3- S benzothiazol-4-yl 27294-(trifluoromethyl)phenyl 2-amino-1,3-benzothiazol- S 4-yl 27304-(trifluoromethyl)phenyl 2-aminoimidazo[1,2- S a]pyridin-8-yl 27314-(trifluoromethyl)phenyl 2-aminoquinazolin-8-yl S 27324-(trifluoromethyl)phenyl 2-aminoquinolin-7-yl S 27334-(trifluoromethyl)phenyl 2-aminoquinolin-8-yl S 27344-(trifluoromethyl)phenyl 2-aminoquinoxalin-5-yl S 27354-(trifluoromethyl)phenyl 2-chloro-1,3-benzothiazol- S 4-yl 27364-(trifluoromethyl)phenyl 2-chloroquinolin-8-yl S 27374-(trifluoromethyl)phenyl 2-hydroxy-1,3- S benzothiazol-4-yl 27384-(trifluoromethyl)phenyl 2-hydroxy-4- S methylquinolin-7-yl 27394-(trifluoromethyl)phenyl 2-hydroxyquinolin-7-yl S 27404-(trifluoromethyl)phenyl 2-hydroxyquinoxalin-5-yl S 27414-(trifluoromethyl)phenyl 2-methyl-1,3-benzothiazol- S 5-yl 27424-(trifluoromethyl)phenyl 2-naphthyl S 2743 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- S tetrahydroquinolin-7-yl 2744 4-(trifluoromethyl)phenyl2-oxo-1,2,3,4- S tetrahydroquinoxalin-5-yl 27454-(trifluoromethyl)phenyl 2-pyridin-4-yl-1,3- S benzothiazol-4-yl 27464-(trifluoromethyl)phenyl 3-(1-hydroxy-1- S methylethyl)quinolin-7-yl2747 4-(trifluoromethyl)phenyl 3-(1-hydroxyethyl)quinolin- S 7-yl 27484-(trifluoromethyl)phenyl 3-(hydroxymethyl)-1,2,3,4- Stetrahydroquinolin-7-yl 2749 4-(trifluoromethyl)phenyl3-(hydroxymethyl)-2-oxo- S 1,2,3,4-tetrahydroquinolin- 7-yl 27504-(trifluoromethyl)phenyl 3-(hydroxymethyl)quinolin- S 7-yl 27514-(trifluoromethyl)phenyl 3- S (methoxycarbonyl)quinolin 7-yl 27524-(trifluoromethyl)phenyl 3,4-dimethyiphenyl S 27534-(trifluoromethyl)phenyl 3-amino-2-oxo-1,2- S dihydroquinoxalin-5-yl2754 4-(trifluoromethyl)phenyl 3-aminoquinoxalin-5-yl S 27554-(trifluoromethyl)phenyl 3-chloro-2-methylphenyl S 27564-(trifluoromethyl)phenyl 3-oxo-1,2,3,4- S tetrahydroisoquinolin-8-yl2757 4-(trifluoromethyl)phenyl 4-(methylamino)quinazolin- S 8-yl 27584-(trifluoromethyl)phenyl 4-aminoquinazolin-8-yl S 27594-(trifluoromethyl)phenyl 4-methylquinolin-8-yl S 27604-(trifluoromethyl)phenyl isoquinolin-5-yl S 27614-(trifluoromethyl)phenyl isoquinolin-8-yl S 27624-(trifluoromethyl)phenyl quinolin-5-yl S 2763 4-(trifluoromethyl)phenylquinolin-7-yl S 2764 4-(trifluoromethyl)phenyl quinolin-8-yl S 27654-(trifluoromethyl)piperidin-1-yl 2-amino-1,3-benzothiazol- S 4-yl 27664-acetylphenyl 2-(acetylamino)-1,3- S benzothiazol-4-yl 27674-acetylphenyl 2-amino-1,3-benzothiazol- S 4-yl 27684-benzylpiperazin-1-yl 2-(acetylamino)-1,3- S benzothiazol-4-yl 27694-bromophenyl quinolin-7-yl S 2770 4-bromophenyl2-amino-1,3-benzothiazol- S 4-yl 2771 4-bromophenyl 2-(acetylamino)-1,3-S benzothiazol-4-yl 2772 4-chlorophenyl quinolin-7-yl S 27734′-fluoro-5-(trifluoromethyl)-1,1′-biphenyl- 2-quinolin-7-yl S yl 27744-fluorophenyl quinolin-7-yl S 2775 4-methylphenyl2-amino-1,3-benzothiazol- S 4-yl 2776 4-methylphenyl2-(acetylamino)-1,3- S benzothiazol-4-yl 2777 4-phenylpiperazin-1-yl2-(acetylamino)-1,3- S benzothiazol-4-yl 27784-tert-butylcyclohex-1-en-1-yl 2-(acetylamino)-1,3- S benzothiazol-4-yl2779 4-tert-butylcyclohex-1-en-1-yl 2-amino-1,3-benzothiazol- S 4-yl2780 4-tert-butylphenyl 2,3-dihydro-1,4- S benzodioxin-6-yl 27814-tert-butylphenyl 1H-1,2,3-benzotriazol-6-yl S 2782 4-tert-butylphenyl3-methoxyphenyl S 2783 4-tert-butylphenyl quinolin-7-yl S 27844-tert-butylphenyl 1,3-benzothiazol-6-yl S 2785 4-tert-butylphenylquinolin-7-yl S 2786 4-tert-butylphenyl 2-methyl-1,3-benzothiazol- S5-yl 2787 4-tert-butylphenyl 2-amino-1,3-benzothiazol- S 4-yl 27884-tert-butylphenyl 2-(acetylamino)-1,3- S benzothiazol-4-ylCapsaicin-Induced Ca2+ Influx in Primary Dorsal Root Ganglion Neurons

Embryonic 19 day old (E19) dorsal root ganglia (DRG) were dissected fromtimed-pregnant, terminally anesthetized Sprague-Dawley rats (CharlesRiver, Wilmington, Mass.) and collected in ice-cold L-15 media (LifeTechnologies, Grand Island, N.Y.) containing 5% heat inactivated horseserum (Life Technologies). The DRG were then dissociated into singlecell suspension using a papain dissociation system (WorthingtonBiochemical Corp., Freehold, N.J.). The dissociated cells were pelletedat 200×g for 5 min and re-suspended in EBSS containing 1 mg/ml ovomucoidinhibitor, 1 mg/ml ovalbumin and 0.005% DNase.

Cell suspension was centrifuged through a gradient solution containing10 mg/ml ovomucoid inhibitor, 10 mg/ml ovalbumin at 200×g for 6 min toremove cell debris; and filtered through a 88-μm nylon mesh (FisherScientific, Pittsburgh, Pa.) to remove any clumps. Cell number wasdetermined with a hemocytometer and cells were seeded intopoly-ornithine 100 μg/ml (Sigma) and mouse laminin 1 μg/ml (LifeTechnologies)-coated 96-well plates at 10×10³ cells/well in completemedium. The complete medium consists of minimal essential medium (MEM)and Ham's F12, 1:1, penicillin (100 U/ml), and streptomycin (100/g/ml),and nerve growth factor (10 ng/ml), 10% heat inactivated horse serum(Life Technologies). The cultures were kept at 37° C., 5% CO₂ and 100%humidity. For controlling the growth of non-neuronal cells,5-fluoro-2′-deoxyuridine (75 μM) and uridine (180 μM) were included inthe medium. Activation of VR1 is achieved in these cellular assays usingeither a capsaicin stimulus (ranging from 0.01-10 μM) or by an acidstimulus (addition of 30 mM Hepes/Mes buffered at pH 4.1). Compounds arealso tested in an assay format to evaluate their agonist properties atVR1.

Capsaicin Antagonist Assay: E-19 DRG cells at 5 days in culture areincubated with serial concentrations of VR1 antagonists, in HBSS (Hanksbuffered saline solution supplemented with BSA 0.1 mg/ml and 1 mM Hepesat pH 7.4) for 15 min, 37° C. Cells are then challenged with a VR1agonist, capsaicin 200 nM, in activation buffer containing 0.1 mg/mlBSA, 15 mM Hepes, pH 7.4, and 10 μCi/ml ⁴⁵Ca²⁺ (Amersham) in Ham's F12for 2 min at 37° C.

Acid Antagonist Assay: Compounds are pre-incubated with E-19 DRG cellsfor 2 minutes prior to addition of Calcium-45 in 30 mM Hepes/Mes buffer(Final Assay pH 5) and then left for an additional 2 minutes prior tocompound washout. Final 45Ca (Amersham CES3-2mCi) at 10 μCi/mL.

Agonist Assay: Compounds are incubated with E-19 DRG cells for 2 minutesin the presence of Calcium-45 prior to compound washout. Final ⁴⁵Ca²⁺(Amersham CES3-2mCi) at 10 μCi/mL.

Compound Washout and Analysis: Assay plates are washed using an ELX405plate washer (Bio-Tek Instruments Inc.) immediately after functionalassay. Wash 3× with PBS Mg2+/Ca2+ free, 0.1 mg/mL BSA. Aspirate betweenwashes. Read plates using a MicroBeta Jet (Wallac Inc.). Compoundactivity is then calculated using appropriate computational algorithms.

⁴⁵Calcium²⁺ Assay Protocol

Compounds may be assayed using Chinese Hamster Ovary cell lines stablyexpressing either human VR1 or rat VR1 under a CMV promoter. Cells canbe cultured in Growth Medium, routinely passaged at 70% confluency usingtrypsin and plated in the assay plate 24 hours prior to compoundevaluation.

Possible Growth Medium:

-   -   DMEM, high glucose (Gibco 11965-084).    -   10% Dialyzed serum (Hyclone SH30079.03).    -   1× Non-Essential Amino Acids (Gibco 11140-050).    -   1× Glutamine-Pen-Strep (Gibco 10378-016).    -   Geneticin, 450 μg/mL (Gibco 10131-035).

Compounds can be diluted in 100% DMSO and tested for activity overseveral log units of concentration [40 μM-2 pM]. Compounds may befurther diluted in HBSS buffer (pH 7.4) 0.1 mg/mL BSA, prior toevaluation. Final DMSO concentration in assay would be 0.5%. Each assayplate can be controlled with a buffer only and a known antagonistcompound (either capsazepine or one of the described VR1 antagonists).

Activation of VR1 can be achieved in these cellular assays using eithera capsaicin stimulus (ranging from 0.1-1CM) or by an acid stimulus(addition of 30 mM Hepes/Mes buffered at pH 4.1). Compounds may alsotested in an assay format to evaluate their agonist properties at VR1.

Capsaicin Antagonist Assay: Compounds may be pre-incubated with cells(expressing either human or rat VR1) for 2 minutes prior to addition ofCalcium-45 and Capsaicin and then left for an additional 2 minutes priorto compound washout. Capsaicin (0.5 nM) can be added in HAM's F12, 0.1mg/mL BSA, 15 mM Hepes at pH 7.4. Final ⁴⁵Ca (Amersham CES3-2 mCi) at 10μCi/mL.

Acid Antagonist Assay: Compounds can be pre-incubated with cells(expressing either human or rat VR1) for 2 minutes prior to addition ofCalcium-45 in 30 mM Hepes/Mes buffer (Final Assay pH 5) and then leftfor an additional 2 minutes prior to compound washout. Final ⁴⁵Ca(Amersham CES3-2 mCi) at 10 μCi/mL.

Agonist Assay: Compounds can be incubated with cells (expressing eitherhuman or rat VR1) for 2 minutes in the presence of Calcium-45 prior tocompound washout. Final ⁴⁵Ca (Amersham CES3-2 mCi) at 10 μCi/mL.

Compound Washout and Analysis: Assay plates can be washed using anELX405 plate washer (Bio-Tek Instruments Inc.) immediately afterfunctional assay. One can wash 3× with PBS Mg2⁺/Ca²⁺ free, 0.1 mg/mLBSA, aspirating between washes. Plates may be read using a MicroBeta Jet(Wallac Inc.). Compound activity may then calculated using appropriatecomputational algorithms.

Useful nucleic acid sequences and proteins may be found in U.S. Pat.Nos. 6,335,180, 6,406,908 and 6,239,267, herein incorporated byreference in their entirety.

For the treatment of vanilloid-receptor-diseases, such as acute,inflammatory and neuropathic pain, dental pain, general headache,migraine, cluster headache, mixed-vascular and non-vascular syndromes,tension headache, general inflammation, arthritis, rheumatic diseases,osteoarthritis, inflammatory bowel disorders, inflammatory eyedisorders, inflammatory or unstable bladder disorders, psoriasis, skincomplaints with inflammatory components, chronic inflammatoryconditions, inflammatory pain and associated hyperalgesia and allodynia,neuropathic pain and associated hyperalgesia and allodynia, diabeticneuropathy pain, causalgia, sympathetically maintained pain,deafferentation syndromes, asthma, epithelial tissue damage ordysfunction, herpes simplex, disturbances of visceral motility atrespiratory, genitourinary, gastrointestinal or vascular regions,wounds, burns, allergic skin reactions, pruritus, vitiligo, generalgastrointestinal disorders, gastric ulceration, duodenal ulcers,diarrhea, gastric lesions induced by necrotising agents, hair growth,vasomotor or allergic rhinitis, bronchial disorders or bladderdisorders, the compounds of the present invention may be administeredorally, parentally, by inhalation spray, rectally, or topically indosage unit formulations containing conventional pharmaceuticallyacceptable carriers, adjuvants, and vehicles. The term parenteral asused herein includes, subcutaneous, intravenous, intramuscular,intrasternal, infusion techniques or intraperitoneally.

Treatment of diseases and disorders herein is intended to also includethe prophylactic administration of a compound of the invention, apharmaceutical salt thereof, or a pharmaceutical composition of eitherto a subject (i.e., an animal, preferably a mammal, most preferably ahuman) believed to be in need of preventative treatment, such as, forexample, pain, inflammation and the like.

The dosage regimen for treating vanilloid-receptor-mediated diseases,cancer, and/or hyperglycemia with the compounds of this invention and/orcompositions of this invention is based on a variety of factors,including the type of disease, the age, weight, sex, medical conditionof the patient, the severity of the condition, the route ofadministration, and the particular compound employed.

Thus, the dosage regimen may vary widely, but can be determinedroutinely using standard methods. Dosage levels of the order from about0.01 mg to 30 mg per kilogram of body weight per day, preferably fromabout 0.1 mg to 10 mg/kg, more preferably from about 0.25 mg to 1 mg/kgare useful for all methods of use disclosed herein.

The pharmaceutically active compounds of this invention can be processedin accordance with conventional methods of pharmacy to produce medicinalagents for administration to patients, including humans and othermammals.

For oral administration, the pharmaceutical composition may be in theform of, for example, a capsule, a tablet, a suspension, or liquid. Thepharmaceutical composition is preferably made in the form of a dosageunit containing a given amount of the active ingredient. For example,these may contain an amount of active ingredient from about 1 to 2000mg, preferably from about 1 to 500 mg, more preferably from about 5 to150 mg. A suitable daily dose for a human or other mammal may varywidely depending on the condition of the patient and other factors, but,once again, can be determined using routine methods.

The active ingredient may also be administered by injection as acomposition with suitable carriers including saline, dextrose, or water.The daily parenteral dosage regimen will be from about 0.1 to about 30mg/kg of total body weight, preferably from about 0.1 to about 10 mg/kg,and more preferably from about 0.25 mg to 1 mg/kg.

Injectable preparations, such as sterile injectable aqueous oroleaginous suspensions, may be formulated according to the known areusing suitable dispersing or wetting agents and suspending agents. Thesterile injectable preparation may also be a sterile injectable solutionor suspension in a non-toxic parenterally acceptable diluent or solvent,for example as a solution in 1,3-butanediol. Among the acceptablevehicles and solvents that may be employed are water, Ringer's solution,and isotonic sodium chloride solution. In addition, sterile, fixed oilsare conventionally employed as a solvent or suspending medium. For thispurpose any bland fixed oil may be employed, including synthetic mono-or diglycerides. In addition, fatty acids such as oleic acid find use inthe preparation of injectables.

Suppositories for rectal administration of the drug can be prepared bymixing the drug with a suitable non-irritating excipient such as cocoabutter and polyethylene glycols that are solid at ordinary temperaturesbut liquid at the rectal temperature and will therefore melt in therectum and release the drug.

A suitable topical dose of active ingredient of a compound of theinvention is 0.1 mg to 150 mg administered one to four, preferably oneor two times daily. For topical administration, the active ingredientmay comprise from 0.001% to 10% w/w, e.g., from 1% to 2% by weight ofthe formulation, although it may comprise as much as 10% w/w, butpreferably not more than 5% w/w, and more preferably from 0.1% to 1% ofthe formulation.

Formulations suitable for topical administration include liquid orsemi-liquid preparations suitable for penetration through the skin(e.g., liniments, lotions, ointments, creams, or pastes) and dropssuitable for administration to the eye, ear, or nose.

For administration, the compounds of this invention are ordinarilycombined with one or more adjuvants appropriate for the indicated routeof administration. The compounds may be admixed with lactose, sucrose,starch powder, cellulose esters of alkanoic acids, stearic acid, talc,magnesium stearate, magnesium oxide, sodium and calcium salts ofphosphoric and sulfuric acids, acacia, gelatin, sodium alginate,polyvinyl-pyrrolidine, and/or polyvinyl alcohol, and tableted orencapsulated for conventional administration. Alternatively, thecompounds of this invention may be dissolved in saline, water,polyethylene glycol, propylene glycol, ethanol, corn oil, peanut oil,cottonseed oil, sesame oil, tragacanth gum, and/or various buffers.Other adjuvants and modes of administration are well known in thepharmaceutical art. The carrier or diluent may include time delaymaterial, such as glyceryl monostearate or glyceryl distearate alone orwith a wax, or other materials well known in the art.

The pharmaceutical compositions may be made up in a solid form(including granules, powders or suppositories) or in a liquid form(e.g., solutions, suspensions, or emulsions). The pharmaceuticalcompositions may be subjected to conventional pharmaceutical operationssuch as sterilization and/or may contain conventional adjuvants, such aspreservatives, stabilizers, wetting agents, emulsifiers, buffers etc.

Solid dosage forms for oral administration may include capsules,tablets, pills, powders, and granules. In such solid dosage forms, theactive compound may be admixed with at least one inert diluent such assucrose, lactose, or starch. Such dosage forms may also comprise, as innormal practice, additional substances other than inert diluents, e.g.,lubricating agents such as magnesium stearate. In the case of capsules,tablets, and pills, the dosage forms may also comprise buffering agents.Tablets and pills can additionally be prepared with enteric coatings.

Liquid dosage forms for oral administration may include pharmaceuticallyacceptable emulsions, solutions, suspensions, syrups, and elixirscontaining inert diluents commonly used in the art, such as water. Suchcompositions may also comprise adjuvants, such as wetting, sweetening,flavoring, and perfuming agents.

Compounds of the present invention can possess one or more asymmetriccarbon atoms and are thus capable of existing in the form of opticalisomers as well as in the form of racemic or non-racemic mixturesthereof. The optical isomers can be obtained by resolution of theracemic mixtures according to conventional processes, e.g., by formationof diastereoisomeric salts, by treatment with an optically active acidor base. Examples of appropriate acids are tartaric, diacetyltartaric,dibenzoyltartaric, ditoluoyltartaric, and camphorsulfonic acid and thenseparation of the mixture of diastereoisomers by crystallizationfollowed by liberation of the optically active bases from these salts. Adifferent process for separation of optical isomers involves the use ofa chiral chromatography column optimally chosen to maximize theseparation of the enantiomers. Still another available method involvessynthesis of covalent diastereoisomeric molecules by reacting compoundsof the invention with an optically pure acid in an activated form or anoptically pure isocyanate. The synthesized diastereoisomers can beseparated by conventional means such as chromatography, distillation,crystallization or sublimation, and then hydrolyzed to deliver theenantiomerically pure compound. The optically active compounds of theinvention can likewise be obtained by using active starting materials.These isomers may be in the form of a free acid, a free base, an esteror a salt.

Likewise, the compounds of this invention may exist as isomers, that iscompounds of the same molecular formula but in which the atoms, relativeto one another, are arranged differently. In particular, the alkylenesubstituents of the compounds of this invention, are normally andpreferably arranged and inserted into the molecules as indicated in thedefinitions for each of these groups, being read from left to right.However, in certain cases, one skilled in the art will appreciate thatit is possible to prepare compounds of this invention in which thesesubstituents are reversed in orientation relative to the other atoms inthe molecule. That is, the substituent to be inserted may be the same asthat noted above except that it is inserted into the molecule in thereverse orientation. One skilled in the art will appreciate that theseisomeric forms of the compounds of this invention are to be construed asencompassed within the scope of the present invention.

The compounds of the present invention can be used in the form of saltsderived from inorganic or organic acids. The salts include, but are notlimited to, the following: acetate, adipate, alginate, citrate,aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate,camphorsulfonate, digluconate, cyclopentanepropionate, dodecylsulfate,ethanesulfonate, glucoheptanoate, glycerophosphate, hemisulfate,heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide,hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate,methansulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, palmoate,pectinate, persulfate, 2-phenylpropionate, picrate, pivalate,propionate, succinate, tartrate, thiocyanate, tosylate, mesylate, andundecanoate. Also, the basic nitrogen-containing groups can bequaternized with such agents as lower alkyl halides, such as methyl,ethyl, propyl, and butyl chloride, bromides and iodides; dialkylsulfates like dimethyl, diethyl, dibutyl, and diamyl sulfates, longchain halides such as decyl, lauryl, myristyl and stearyl chlorides,bromides and iodides, aralkyl halides like benzyl and phenethylbromides, and others. Water or oil-soluble or dispersible products arethereby obtained.

Examples of acids that may be employed to from pharmaceuticallyacceptable acid addition salts include such inorganic acids ashydrochloric acid, sulfuric acid and phosphoric acid and such organicacids as oxalic acid, maleic acid, succinic acid and citric acid. Otherexamples include salts with alkali metals or alkaline earth metals, suchas sodium, potassium, calcium or magnesium or with organic bases.

Also encompassed in the scope of the present invention arepharmaceutically acceptable esters of a carboxylic acid or hydroxylcontaining group, including a metabolically labile ester or a prodrugform of a compound of this invention. A metabolically labile ester isone which may produce, for example, an increase in blood levels andprolong the efficacy of the corresponding non-esterified form of thecompound. A prodrug form is one which is not in an active form of themolecule as administered but which becomes therapeutically active aftersome in vivo activity or biotransformation, such as metabolism, forexample, enzymatic or hydrolytic cleavage. For a general discussion ofprodrugs involving esters see Svensson and Tunek Drug Metabolism Reviews165 (1988) and Bundgaard Design of Prodrugs, Elsevier (1985). Examplesof a masked carboxylate anion include a variety of esters, such as alkyl(for example, methyl, ethyl), cycloalkyl (for example, cyclohexyl),aralkyl (for example, benzyl, p-methoxybenzyl), andalkylcarbonyloxyalkyl (for example, pivaloyloxymethyl). Amines have beenmasked as arylcarbonyloxymethyl substituted derivatives which arecleaved by esterases in vivo releasing the free drug and formaldehyde(Bungaard J. Med. Chem. 2503 (1989)). Also, drugs containing an acidicNH group, such as imidazole, imide, indole and the like, have beenmasked with N-acyloxymethyl groups (Bundgaard Design of Prodrugs,Elsevier (1985)). Hydroxy groups have been masked as esters and ethers.EP 039,051 (Sloan and Little, Apr. 11, 1981) discloses Mannich-basehydroxamic acid prodrugs, their preparation and use. Esters of acompound of this invention, may include, for example, the methyl, ethyl,propyl, and butyl esters, as well as other suitable esters formedbetween an acidic moiety and a hydroxyl containing moiety. Metabolicallylabile esters, may include, for example, methoxymethyl, ethoxymethyl,iso-propoxymethyl, α-methoxyethyl, groups such asα-((C₁-C₄)alkyloxy)ethyl, for example, methoxyethyl, ethoxyethyl,propoxyethyl, iso-propoxyethyl, etc.; 2-oxo-1,3-dioxolen-4-ylmethylgroups, such as 5-methyl-2-oxo-1,3,dioxolen-4-ylmethyl, etc.; C₁-C₃alkylthiomethyl groups, for example, methylthiomethyl, ethylthiomethyl,isopropylthiomethyl, etc.; acyloxymethyl groups, for example,pivaloyloxymethyl, α-acetoxymethyl, etc.; ethoxycarbonyl-1-methyl; orα-acyloxy-α-substituted methyl groups, for example α-acetoxyethyl.

Further, the compounds of the invention may exist as crystalline solidswhich can be crystallized from common solvents such as ethanol,N,N-dimethylformamide, water, or the like. Thus, crystalline forms ofthe compounds of the invention may exist as polymorphs, solvates and/orhydrates of the parent compounds or their pharmaceutically acceptablesalts. All of such forms likewise are to be construed as falling withinthe scope of the invention.

While the compounds of the invention can be administered as the soleactive pharmaceutical agent, they can also be used in combination withone or more compounds of the invention or other agents. Whenadministered as a combination, the therapeutic agents can be formulatedas separate compositions that are given at the same time or differenttimes, or the therapeutic agents can be given as a single composition.

The foregoing is merely illustrative of the invention and is notintended to limit the invention to the disclosed compounds. Variationsand changes which are obvious to one skilled in the art are intended tobe within the scope and nature of the invention which are defined in theappended claims.

From the foregoing description, one skilled in the art can easilyascertain the essential characteristics of this invention, and withoutdeparting from the spirit and scope thereof, can make various changesand modifications of the invention to adapt it to various usages andconditions.

1. A compound having the structure:

or any pharmaceutically-acceptable salt or hydrate thereof, wherein: Jis NH, O or S; X is N or C(R²); Y is N or C(R³), wherein at least one ofX and Y is N; Z is C(R^(d)), or if X is C(R²), then Z is N or C(R^(d));n is independently, at each instance, 0, 1 or 2; R¹ is a saturated,partially-saturated or unsaturated 5-, 6- or 7-membered monocyclic or6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fused bicyclic ringcontaining 0, 1, 2, 3 or 4 atoms selected from N, O and S, so long asthe combination of O and S atoms is not greater than 2, wherein thecarbon atoms of the ring are substituted by 0, 1 or 2 oxo or thioxogroups, wherein the ring is substituted by 0, 1, 2, 3 or 4 substituentsselected from C₁₋₈alkyl, halo, C₁₋₄haloalkyl, cyano, nitro, —C(═O)R^(e),—C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R²)C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(h), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 saturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groupsselected from R^(e), halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR¹,—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—C(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(f),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 C₁₋₄alkyl groups substituted by 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —C(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h) wherein R¹ is not tetrazole; R² is,independently, in each instance, selected from H, C₁₋₈alkyl, halo,C₁₋₄haloalkyl, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); or R² is a saturated, partially-saturated orunsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 0, 1, 2, 3 or 4atoms selected from N, O and S, so long as the combination of O and Satoms is not greater than 2, wherein the carbon atoms of the ring aresubstituted by 0, 1 or 2 oxo or thioxo groups, wherein the ring issubstituted by 0, 1, 2 or 3 groups selected from R^(e), halo, cyano,nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); or R² is C₁₋₄alkyl substituted by 0, 1, 2 or 3groups selected from C₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); R³ is, independently, in each instance, H, halo,—NH₂, —NHC₁₋₃alkyl, —N(C₁₋₃alkyl)C₁₋₃alkyl, or C₁₋₃alkyl; R⁴ is asaturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2, 3 or 4substituents selected from C₁₋₈alkyl, C₁₋₄haloalkyl, halo, cyano, nitro,—C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),—OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e),,OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), -s(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f), —S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂ NR^(a)R^(f),—NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f), —N an h; andthe ring may —NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h);and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a),R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f), —NR^(f)C₂₋₆alkylOR^(f),—C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h),—OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),,—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h) wherein R⁴ is not pyrrolidine or pyrazole; R^(a)is independently, at each instance, H, phenyl, benzyl or C₁₋₆alkyl, thephenyl, benzyl and C₁₋₆alkyl being substituted by 0, 1, 2 or 3substituents selected from halo, C₁₋₄alkyl, C₁₋₃haloalkyl, —OC₁₋₄alkyl,—NH₂, —NHC₁₋₄alkyl, —N(C₁₋₄alkyl)C₁₋₄alkyl; R^(d) is independently ineach instance hydrogen or —CH₃; R^(e) is, independently, in eachinstance, C₁₋₉alkyl or C₁₋₄alkyl(phenyl) wherein either is substitutedby 0, 1, 2, 3 or 4 substituents selected from halo, C₁₋₄haloalkyl,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(e), —C(═O)NR^(a)R^(a),—C(═NR^(a))NR^(a)R^(a), —OR^(a), —OC(═O)R^(e), —OC(═O)NR^(a)R^(a),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(a), —OC₂₋₆alkylOR^(a),—SR^(a), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(a),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(e),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(a), —NR^(a)R^(a), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(e), —N(R^(a))C(═O)NR^(a)R^(a),—N(R^(a))C(═NR^(a))NR^(a)R^(a), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(a), —NR^(a)C₂₋₆alkylNR^(a)R^(a) and—NR^(a)C₂₋₆alkylOR^(a); and wherein the C₁₋₉alkyl is additionallysubstituted by 0 or 1 groups independently selected from R^(h); R^(f)is, independently, in each instance, R^(e) or H; R⁹ is, independently,in each instance, a saturated or unsaturated 5- or 6-membered monocyclicring containing 1, 2 or 3 atoms selected from N, O and S, so long as thecombination of O and S atoms is not greater than 2, wherein the ring issubstituted by 0 or 1 oxo or thioxo groups; and R^(h) is, independently,in each instance, phenyl or a saturated or unsaturated 5- or 6-memberedmonocyclic ring containing 1, 2 or 3 atoms selected from N, O and S, solong as the combination of O and S atoms is not greater than 2, whereinthe ring is substituted by 0 or 1 oxo or thioxo groups, wherein thephenyl or monocycle are substituted by 0, 1, 2 or 3 substituentsselected from halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(e),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR¹, —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(f), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(e), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(e),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f) and —NR^(a)C₂₋₆alkylOR^(f).
 2. A compoundaccording to claim 1, wherein X is C(R²); Y is N; and Z is C(R^(d)). 3.A compound according to claim 1, wherein X is C(R²); Y is N; and Z is N.4. A compound according to claim 1, wherein X is N; Y is N; and Z isC(R^(d)).
 5. A compound according to claim 1, wherein X is N; Y isC(R³); and Z is C(R^(d)).
 6. A compound according to claim 1, wherein R¹is a saturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic ring containing 0, 1, 2 or 3 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2, 3 or 4substituents selected from C₁₋₈alkyl, halo, C₁₋₄haloalkyl, cyano, nitro,—C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f),—OR^(f), —OC(═O)R^(e), —C(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —C(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 saturated, partially-saturated or unsaturated 5-, 6- or 7-memberedmonocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered vicinally-fusedbicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S,so long as the combination of O and S atoms is not greater than 2,wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo orthioxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groupsselected from R^(e), halo, cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f),—C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e),—OC(═O)NR^(a)R^(f), —OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f),—OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e), —S(═O)₂R^(e),—S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(a))C(═O)R^(e), —N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring is additionally substituted by 0 or1 C₁₋₄alkyl groups substituted by 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).
 7. A compound according to claim 1, wherein R⁴is a saturated, partially-saturated or unsaturated 8-, 9-, 10- or11-membered vicinally-fused bicyclic ring containing 1 N atom and 0, 1,2, or 3 additional atoms selected from N, O and S, so long as thecombination of O and S atoms is not greater than 2, wherein the carbonatoms of the ring are substituted by 0, 1 or 2 oxo or thioxo groups,wherein the ring is substituted by 0, 1, 2, 3 or 4 substituents selectedfrom C₁₋₈alkyl, C₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e),—C(═O)OR², —C(═O)NR^(a)R^(f), —C(═NR^(a))NR^(a)R^(f), —OR^(f),—OC(═O)R^(e), —OC(═O)NR^(a)R^(f), —OC(═O)N(R^(f))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f), —SR^(e), —S(═O)R^(e),—S(═O)₂R^(e), ,S(═O)₂NR^(a)R^(f), —S(═O)₂N(R^(f))C(═O)R^(e),—S(═O)₂N(R^(f))C(═O)OR^(f).—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f),—NR^(a)R^(f), —N(R^(f))C(═O)R^(e), —N(R^(f))C(═O)OR^(f),—N(R^(f))C(═O)NR^(a)R^(f), —N(R^(f))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(f))S(═O)₂NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)R^(h),—C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(h), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(h),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h); and the ring may be additionally substuted byC₁₋₄alkyl substituted by 1, 2 or 3 substituents selected from halo,cyano, nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(f))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(f))C(═O)R^(e), —S(═O)₂N(R^(f))C(═O)OR^(f),—S(═O)₂N(R^(f))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(f))C(═O)R^(e),—N(R^(f))C(═O)OR^(f), —N(R^(f))C(═O)NR^(a)R^(f),—N(R^(f))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(f))S(═O)₂NR^(a)R^(f), —NR^(f)C₂₋₆alkylNR^(a)R^(f),—NR^(f)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(═O)OR^(h), —C(═O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).
 8. A compound according to claim 1, wherein R²is H.
 9. A compound according to claim 1, wherein R² is, independently,in each instance, selected from C₁₋₈alkyl, halo, C₁₋₄haloalkyl, cyano,nitro, —C(═O)R^(e), —C(═O)OR^(f), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f), —N(R^(a))C(═O)NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(f), —N(R^(a))S(═O)₂R^(e),—N(R^(a))S(═O)₂NR^(a)R^(f), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h), —C(O)OR^(h), —C(O)NR^(a)R^(h),—C(═NR^(a))NR^(a)R^(h), —OR^(h), —OC(═O)R^(h), —OC(═O)NR^(a)R^(h),—OC(═O)N(R^(a))S(═O)₂R^(h), —OC(═O)N(R^(h))S(═O)₂R^(e),—OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h), —SR^(h), —S(═O)R^(h),—S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h), —S(═O)₂N(R^(h))C(═O)R^(e),—S(═O)₂N(R^(a))C(═O)R^(h), —S(═O)₂N(R^(h))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)OR^(h), —S(═O)₂N(R^(h))C(═O)NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(h), —NR^(a)R^(h), —N(R^(h))C(═O)R^(e),—N(R^(a))C(═O)R^(h), —N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h),—N(R^(h))C(═O)NR^(a)R^(f), —N(R^(a))C(═O)NR^(a)R^(h),—N(R^(h))C(═NR^(a))NR^(a)R^(f), —N(R^(a))C(═NR^(a))NR^(a)R^(h),—N(R^(h))S(═O)₂R^(e), —N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(h)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).
 10. A compound according to claim 1, wherein R²is C₁₋₄alkyl substituted by 0, 1, 2 or 3 groups selected fromC₁₋₄haloalkyl, halo, cyano, nitro, —C(═O)R^(e), —C(═O)NR^(a)R^(f),—C(═NR^(a))NR^(a)R^(f), —OR^(f), —OC(═O)R^(e), —OC(═O)NR^(a)R^(f),—OC(═O)N(R^(a))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(f), —OC₂₋₆alkylOR^(f),—SR^(e), —S(═O)R^(e), —S(═O)₂R^(e), —S(═O)₂NR^(a)R^(f),—S(═O)₂N(R^(a))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)OR^(f),—S(═O)₂N(R^(a))C(═O)NR^(a)R^(f), —NR^(a)R^(f), —N(R^(a))C(═O)R^(e),—N(R^(a))C(═O)OR^(f),—N(R^(a))C(═O)NR^(a)R^(f).—N(R^(a))C(═NR^(a))NR^(a)R^(f),—N(R^(a))S(═O)₂R^(e), —N(R^(a))S(═O)₂NR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(f), —NR^(a)C₂₋₆alkylOR^(f), —C(═O)R^(h),—C(═O)OR^(h), —C(═O)NR^(a)R^(h), —C(═NR^(a))NR^(a)R^(h), —OR^(h),—OC(═O)R^(h), —OC(═O)NR^(a)R^(h), —OC(═O)N(R^(a))S(═O)₂R^(h),—OC(═O)N(R^(h))S(═O)₂R^(e), —OC₂₋₆alkylNR^(a)R^(h), —OC₂₋₆alkylOR^(h),—SR^(h), —S(═O)R^(h), —S(═O)₂R^(h), —S(═O)₂NR^(a)R^(h),—S(═O)₂N(R^(h))C(═O)R^(e), —S(═O)₂N(R^(a))C(═O)R^(h),—S(═O)₂N(R^(h))C(═O)OR^(f), —S(═O)₂N(R^(a))C(═O)OR^(h),—S(═O)₂N(R^(h))C(═O)NR^(a)R^(f), —S(═O)₂N(R^(a))C(═O)NR^(a)R^(h),—NR^(a)R^(h), —N(R^(h))C(═O)R^(e), —N(R^(a))C(═O)R^(h),—N(R^(h))C(═O)OR^(f), —N(R^(a))C(═O)OR^(h), —N(R^(h))C(═O)NR^(a)R^(f),—N(R^(a))C(═O)NR^(a)R^(h), —N(R^(h))C(═NR^(a))NR^(a)R^(f),—N(R^(a))C(═NR^(a))NR^(a)R^(h), —N(R^(h))S(═O)₂R^(e),—N(R^(a))S(═O)₂R^(h), —N(R^(h))S(═O)₂NR^(a)R^(f),—N(R^(a))S(═O)₂NR^(a)R^(h), —NR^(a)C₂₋₆alkylNR^(a)R^(f),—NR^(a)C₂₋₆alkylNR^(a)R^(h), —NR^(h)C₂₋₆alkylOR^(f) and—NR^(a)C₂₋₆alkylOR^(h).
 11. A compound selected from the group of:4-[5-(4-trifluoromethyl-phenyl)-pyridin-3-yloxy]-benzothiazol-2-ylamine;N-{4-[5-(4-trifluoromethyl-phenyl)-pyridin-3-yloxy]-benzothiazol-2-yl}-acetamide;4-[6-(4-trifluoromethyl-phenyl)-pyrazin-2-yloxy]-benzothiazol-2-ylamine;N-{4-[6-(4-trifluoromethyl-phenyl)-pyrazin-2-yloxy]-benzothiazol-2-yl}-acetamide;(2,3-dihydro-benzo[1,4]dioxin-6-yl)-[2-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-amine;and 7-[5-(4-Trifluoromethyl-phenyl)-pyridin-3-yloxy]-quinoline, or anypharmaceutically-acceptable salts or hydrates thereof.
 12. Apharmaceutical composition comprising a compound according to claim 1and a pharmaceutically-acceptable diluent or carrier.
 13. A method oftreating acute, inflammatory and neuropathic pain, dental pain, generalheadache, migraine, cluster headache, mixed-vascular and non-vascularsyndromes, tension headache, general inflammation, arthritis, rheumaticdiseases, osteoarthritis, inflammatory bowel disorders, inflammatory eyedisorders, inflammatory or unstable bladder disorders, psoriasis, skincomplaints with inflammatory components, chronic inflammatoryconditions, inflammatory pain and associated hyperalgesia and allodynia,neuropathic pain and associated hyperalgesia and allodynia, diabeticneuropathy pain, causalgia, sympathetically maintained pain,deafferentation syndromes, asthma, epithelial tissue damage ordysfunction, herpes simplex, disturbances of visceral motility atrespiratory, genitourinary, gastrointestinal or vascular regions,wounds, burns, allergic skin reactions, pruritus, vitiligo, generalgastrointestinal disorders, gastric ulceration, duodenal ulcers,diarrhea, gastric lesions induced by necrotising agents, hair growth,vasomotor or allergic rhinitis, bronchial disorders or bladderdisorders, comprising the step of administering a compound according toclaim 1.